Victor Frankenstein (Charlie Tahan) is an elementary school-aged boy living in quaint, suburban "New Holland." His simple family consists of himself, his father Ben Frankenstein (Martin Short), his mother Susan Frankenstein (Catherine O'Hara), and the loyal family dog Sparky. Victor has produced a new '50s style monster movie, starring Sparky as the monster that flattens Victor's handmade, cardboard town, populated with his toys and action figures. Ben and Susan applaud as the movie comes to an end, but Ben tells Susan he wishes Victor would be more like a normal kid, and spend less time making monster movies.
The following morning Victor packs up for school, puts the excitable Sparky in the backyard, and waves to his next-door neighbor and classmate Elsa Van Helsing (Winona Ryder). Elsa's overbearing and obese uncle, Mr. Burgemeister (Martin Short), the mayor of New Holland, chides Elsa, and reminds her to better hold herself, because she will be the star of "Dutch Days" -- New Holland's new annual carnival, which was Mr. Burgemeister's idea. The depressed Elsa agrees to not embarrass him too much. At school, Victor and his classmates are surprised to have a new substitute science teacher, Mr. Rzykruski (Martin Landau), who is replacing their former teacher who is still recovering from a near-fatal lightning strike. "The Weird Girl" (Catherine O'Hara) in Victor's class points out that lightning strikes, while rare in most of the world, are especially common in New Holland, and infers that it might have something to do with the town's centerpiece: a ghostly windmill that sits on a hill in the center of town. Mr. Rzykruski is an especially eccentric western-European immigrant, with a stark, demented affection for science. His passion for science is electric, and his students feel it too. All the students eagerly dream of ideas for their upcoming science fair projects. They all want to win.
The school bell rings, and Victor walks to his bike, and finds "The Weird Girl" waiting for him, cradling her creepy-eyed, Persian cat. She tells him that her cat Whiskers has a special power. It can predict the future through its excrement. She unveils a dry cat-turd, which she had been carrying, which forms the letter "V." She explains that when classmate Toshiaki (James Hiroyuki Liao) pitched a no-hitter in baseball, the night before Whiskers pooped-out a "T." When obese classmate Bob (Robert Capron) injured himself by falling into an open manhole, Whiskers pooped a "B." When spooky classmate Nassor got knocked-out cold by a fastball while playing catcher, Whiskers pooped out an "N." Victor refuses to accept the "V" from the Weird Girl, and bicycles home. When he arrives he finds hunchbacked classmate Edgar "E" Gore (Atticus Shaffer) waiting for him. Edgar begs Victor to be his science project partner. Victor declines the offer, saying that he likes to work by himself. Edgar is annoyed, and leaves. At dinner, Victor asks his parents to sign his permission slip for the science fair. Ben agrees to sign the form only if Victor also signs up for baseball, and gets out of the house once in a while. Edgar agrees, and the form is signed.
The following day Victor, Sparky, and the Frankensteins go to Victor's first baseball game. Toshiaki is pitching, and Victor is at bat. Toshiaki rockets the first two pitches past Victor, but Victor manages to smack the stuffing out of the third. The ball soars out of the park, and Sparky runs after it. The ball rolls across the street and comes to a rest in the gutter. Victor runs after Sparky, but as Sparky is about to return to the field, he's hit by a passing car. Victor, now seeing Whiskers's omen for what it is, cries as Sparky dies in the road. Sparky is given a somber funeral at the New Holland Pet Cemetery. He is buried beneath a dog bone headstone, in a cardboard box.
The next few days are extra hard on Victor, who is still distracted by Sparky's demise. In science class he mostly makes doodles of Sparky, while ignoring Mr. Rzykruski's lesson. Mr. Rzykruski explains that almost all creatures's bodies run on electric impulses, even after they die. To demonstrate, Mr. Rzykruski produces a dead, pinned-down frog. He attaches a pair of wired clamps to each of the frog's legs and flicks a switch. White-hot electricity jumps from the frog's body, and its legs leap up and down. Victor looks on in awe, and immediately draws crude lightning bolts around the doodle of Sparky. Victor sneaks into the New Holland Pet Cemetery, and digs up Sparky's remains. He sneaks home, past his parents, and up to his room. He collects various bits of electrical equipment from around the house and assembles a crude laboratory in the attic. He places Sparky on a platter and raises him up through the attic skylight. Next door, Mr. Burgemeister watches in disgusted curiosity as Victor lets fly a trio of kites into the storm. Victor returns to the attic and watches as lightning strikes near Sparky's body. A bolt strikes Sparky, and bright electrical sparks flow through the attic. As the effects of the strike dissipate, Victor reels in Sparky's body, and checks for signs of life. He finds none. Saddened, Victor hugs Sparky's remains, and feels his tail movie. Sparky, though scarred from the accident, and stapled all over, is alive. He wags his tail with glee, until it falls off.
Over the next few days, Victor keeps Sparky's reanimation a secret from his family and classmates. He pleads with Sparky to stay in the attic while he's at school. The Weird Girl's cat, Whiskers, appears in the attic skylight and calls to Sparky. Sparky chases Whiskers out through the skylight, and into the neighbor's yard where Bob's mother (Conchata Ferrell) is hanging bed sheets. She catches sight of the decomposing Sparky and retreats into her house. Sparky spends the rest of the day outside. He flirts with Elsa's poodle Persephone, and by touching noses, gives it a shocking Bride of Frankenstein-like white streak in her hair. He manages to go mostly unnoticed, with the exception of Edgar, who spots him on the way home from school. Victor returns home and finds Edgar waiting for him. Edgar blackmails Victor, and threatens to tell the whole town about Sparky, unless Victor gives him what he wants -- a science fair project. Edgar visits the local pet shop, and buys the only dead goldfish in the store. He makes Victor reproduce the experiment which reanimated Sparky. A storm gathers, the kites are sent up into the sky, and a single lightning bolt electrifies the fishbowl with the floating, dead fish. They lower the bowl into the attic, but it's empty. Edgar runs his fingers through the water and infers that the fish has to be in there, because he can feel it. The two shine a light into the bowl, and barely see a nearly invisible living skeleton swimming in the water. Their experiment somehow turned the fish invisible. Victor is confused by the results, but Edgar is pleased. An invisible fish will surely win him first place at the science fair. Edgar returns home with the fish, only after promising Victor that he won't tell the class how the fish turned invisible. Victor notices that Sparky is less animated than before, and his eyes are no longer glowing with electricity. He clamps Sparky's bolts to a pair of jumper cables, and plugs him into a wall socket. This immediately returns life to Sparky.
At school, Edgar has broken his promise, and tells everybody about his reanimated, invisible fish. Bob and Toshiaki are most annoyed by this news, because their own science fair project (an off-the-shelf experiment) can't compete with an invisible fish. They vow to come up with something mind-blowing. Later that day, Nassor (Martin Short) asks Edgar to show him the fish. He runs his fingers through the water, and feeling nothing, infers that Edgar's invisible fish is fake and teases him for wasting his time. Bob and Toshiaki, intent upon winning first prize at the science fair, have begun a new experiment involving a carbonated water jetpack, worn by Bob. The pair stand on Bob's roof and Toshiaki pulls the ripcord. The jetpack sends Bob slowly rolling across the roof, briefly gives him the power of flight, and then drops him like of a sack of potatoes. With his arm broken, Bob's mother phones the hospital and the school.
Mr. Rzykruski is in trouble, for encouraging children to engage in dangerous science experiments. Nearly all of the kids's parents support Mr. Rzykruski's firing, with the exception of the Frankensteins, and Mayor Burgemeister fires Mr. Rzykruski in an instant. Victor watches as Mr. Rzykruski takes a cardboard box full of his possessions out to his car, and stops him before he leaves. Victor apologizes for his firing, and asks if an identical experiment can produce two different results. Mr. Rzykruski implies that Victor's experiments had different intents, and therefore, different variables, which affected the outcome. He tells him that science doesn't just take place in one's head, but in one's heart, too. Mr. Rzykruski drives off.
By now, Victor is having a hard time keeping Sparky's reanimation a secret from anyone. Ben and Susan find out and are immediately upset with Victor. During the fight, Sparky escapes the attic and flees the house. The family sets out after him. With the house empty, Edgar, Nassor, Bob, Toshiaki, and the Weird Girl (along with Whiskers) sneak in and take note of Victor's makeshift laboratory. They observe the details and head their separate ways. Edgar breaks into the school's science room, and reproduces Victor's lab with makeshift equipment. He seeks to reanimate a dead rat he found in the school. Nassor and Toshiaki head to the pet cemetery. Toshiaki digs up his recently deceased pet turtle "Shelly" and returns home with the body. Nassor enters an elaborate crypt, and comes to a massive coffin at its center, with a plaque for "Colossus." Bob returns home and empties dozens of bags of Sea Monkeys into his swimming pool. The Weird Girl, with Whiskers, procures a dead bat. The children individually produce their own makeshift Jacob's Ladders and point them into the sky. Lightning strikes them all. Edgar's rat is seemingly pulverized, and Edgar flees the school when he hears the gym teacher walking through the hallway. Toshiaki's turtle, Shelly, had been shocked along with a bottle of Miracle Grow and disappeared after the strike. Nassor waits at the entrance to the crypt, while a huge, hulking shadow makes its way up the stairs. Whiskers, halfway through the strike, started playing with the dead bat, and the pair were electrocuted together. The gym teacher, at the school, is suddenly attacked by a five-feet tall, bipedal, ferocious rat (the result of Edgar's experiment). It chases the gym teacher outside and runs away. "Shelly" has grown to massive, Godzilla-like proportions, and nearly flattens Toshiaki as it stomps through the neighborhood. Bob's swimming pool glows blue with electricity, and dozens of three-feet tall, Gremlin-like Sea Monkeys emerge from the water and terrorize the neighborhood. Nassor's "Colossus" is a tiny, slow-moving hamster. Whiskers has somehow fused with the bat -- the cat's appendages grow long, and disgusting black wings unfurl from its back. It takes off into the night, shrieking awfully.
Victor arrives at the cemetery, where he finds Sparky nestling his grave. Victor carefully approaches him, and the pair make up. Victor sees recently dug-up graves for Shelly and Colossus and soon hears panicked screams coming from the town's Dutch Fair. At the fair, Mayor Burgemeister is forcing Elsa Van Helsing to sing a drab song about Dutch Days, whilst wearing a crown of burning candles on her head. The carnival's opening ceremony is upset by the appearance of Shelly, the Sea Monkeys, Edgar's Rat Monster, and to a lesser degree, Colossus. Victor and co. arrive and are first able to subdue the Sea Monkeys by giving them salty popcorn, which causes them to explode, covering Bob in green goop. The Rat Monster tries attacking Sparky, but bites down on his electric neck bolts, and electrocutes himself back to death. Toshiaki and Nassor, still bitter classroom competitors, pose their monsters against one another. Colossus is easily squished by Shelly's massive foot. Toshiaki films the anticlimactic battle from the carnival's ferris wheel, but is soon threatened by Shelly. Shelly stands in a puddle of spilled beer, and is electrocuted by a nearby spark. She dies and returns to her original size. The townspeople, intent upon destroying all the monsters, see Sparky and chase him from the fairgrounds. Bat-Whiskers arrives, grabs Elsa and Persephone, and escapes to the windmill at the center of town. Victor chases after them.
Bat-Whiskers holds Elsa and Persephone hostage in the top of the windmill, and Victor arrives to save them. Outside the townspeople have arrived, after chasing Sparky, and are waving flaming torches. Mayor Bergermeister threatens Sparky to give-up Elsa, before accidentally setting the windmill on fire. Victor, Elsa, Persephone, and Sparky battle Bat-Whiskers on the face of the burning windmill. All but Sparky and Bat-Whiskers manage to escape to safety. Inside the burning building, Sparky defends himself from the vastly stronger Bat-Whiskers. A piece of flaming debris falls from high and manages to skewer Bat-Whiskers down the middle, killing it. Sparky is buried by the collapsing windmill. Victor cries for Sparky. As the flames settle, Sparky's body is rescued from the debris and brought out to Victor. The townspeople collectively join jumper cables in the parking lot, and hook them up to Sparky's body. They rev their engines all at once and send fresh electricity into Sparky's body. He continues to lay there, motionless. Victor, willing to accept Sparky's fate, bids him farewell and returns to his parents. Sparky slowly comes to, alive, and barks excitedly. Victor is overjoyed, and Persephone and Sparky share a brief romantic spark.
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