NOTE: this spoiler was sent in by John Blackwell.
The opening credits establish the background of Dirk Pitt [Matthew McConaughey], the movie's hero. Dirk Pitt (in case you are not familiar with the works of Clive Cussler) is kind of a Jacques Cousteau / Indiana Jones / James Bond composite. A former Navy SEAL, Dirk Pitt works for NUMA (the National Underwater and Marine Agency) searching for historical shipwrecks and sunken treasures. Usually his expeditions lead to deadly world peril and/or attempts at global domination. (That last point wasn't specifically called out in the opening credits, but you can consider it a spoiler for every movie made in this franchise.)
The opening scene takes place at the siege of Richmond during the American Civil War. Men are loading heavy boxes onto the CSS Texas, a Confederate ironclad. Union cannonballs rain down as the crew struggles to get the Texas loaded and underway. As the Texas sails away, the Union shells bounce harmlessly off.
The scene changes to the present day, where two WHO (World Health Organization) doctors, Dr. Eva Rojas [Penelope Cruz] and Dr. Hopper [Glynn Turman], are investigating a mysterious illness in Lagos, Nigeria. Dr. Rojas heads out alone to a lighthouse to look for another possible victim, where she is attacked by an unknown man. She loses consciousness just after being saved by a harpoon-wielding stranger (Dirk Pitt).
She awakens on a NUMA boat where she meets Al Giordino [Steve Zahn], the sidekick to Dirk Pitt. NUMA is recovering a precious, delicate artifact, which is not so precious that Dirk Pitt can't stand on top of it as it is raised from the water. However, Dirk Pitt's main interest in Nigeria is the source of a confederate gold piece he has acquired. He thinks the CSS Texas sailed across the Atlantic and is waiting to be discovered somewhere in Africa.
The trail to the Texas leads to Mali as does the source of the mysterious illness tracked by the WHO doctors. The doctors pick up land transportation in Mali, while Dirk Pitt, Al Giordino and Rudi Gunn [Rainn Wilson] (NUMA's resident technogeek) set off on expedition up the Niger River.
While making their way up the river, Rudi takes samples of an unusual red algae. Government troops attack the NUMA group by boat and truck. (You can hear the score kick into heavy James Bond mode at this point.) Rudi takes out the truck with a flare gun while Dirk and Al use a rather unlikely plan that involves cutting the fuel lines, propping a lit cigar close to the spurting fuel and jumping off before the boat explodes next to the attacking government boat. Of course it all goes off without a hitch. After climbing from the river, Dirk and Al dress up as tribemen and head off on camels, while Rudi is sent back to report to NUMA's chief, Admiral James Sandecker [William H. Macy].
Meanwhile, the doctors are checking out a sickness-ravaged village. Dr. Rojas descends into the filled-in village well to take samples of the water under the well's bottom. While she is down there, she remembers the creepy video tape she had seen one week earlier showing a ghostly little girl. Wait... Rewind. While she is down there, government troops attack, killing the doctors' driver and holding Dr. Hopper hostage. General Kazim [Lennie James] arrives in his helicopter and demands to know the wherabouts of Dr. Rojas. Dr. Hopper feigns ignorance and is shot dead. General Kazim then flies off, leaving his men to search the village. Dr. Rojas clings to the shadows at the bottom of the well and hopes not to be seen while the soldiers prepare to fire a few warning shots down into the well. Dirk and Al have meanwhile been observing the village from nearby cover. They attack the government troops, kill them all and rescue Dr. Rojas.
While driving away through a valley, Dirk stops the jeep and orders everyone to drop their weapons and exit. Touareg tribesmen descend on Dirk, Al and Dr. Rojas, but seem friendly after Dirk explains that he is no friend of the government. At the Touareg village, Dr. Rojas finds more victims of the mysterious illness and realizes that the source of the sickness is poison from the water supply and not a biological agent. Dirk and Al are also surprised to find that the village contains an antique roadster (stolen from General Kazim) and an old cave painting depicting the CSS Texas. The cave painting shows the Texas next to a large structure, and Dirk and Al set out to find it.
When Dirk and Al find the site of the ancient structure, they are surprised to find a large modern complex nearby. A large solar-collector array is focusing sunlight onto a central tower, but strangely, there is no sign of the electrical lines that a power plant would need. The group hitches a ride on an incoming train to get into the complex and discovers that the facility is actually a waste-disposal plant, using solar energy to incinerate toxic waste. They do have a backup of waste in the basement though, which turns out to be the source of the poisoned wells in the area. The plant uses Touareg slaves captured by the govenment to handle the toxins. Dirk, Al and Dr. Rojas are captured immediatly after learning these facts. The owner (operator?) of the plant turns out to be someone introduced earlier, Massarde [Lambert Wilson], who is pretty much the same eurotrashy character the actor played in the Matrix movies (the Merovingian).
Rudi finally makes his way back to Admiral Sandecker. After testing the algae and running some models, Rudy and the admiral contact the local U.S. ambassador and tell him that the algal bloom will destroy all life on the planet if allowed to reach the ocean. The Ambassador tells them that there is nothing he can do.
Dirk and Al wake up chained to the bed of a speeding truck. Using his confederate gold piece as a screwdriver, Dirk loosens the truck's bed liner, and he and Al manage to eject themselves and the bed liner from the back of the truck. They are still chained to the bed liner, however, and have to carry it. After trudging through the desert, they come upon a wrecked plane. In a funny scene (spoiled by the ads for the movie), they speculate about finding a toolbox in the wreckage, and one of them comments that they probably won't be able to fix the plane. The scene immediatly shifts to them zipping across the desert on the plane, which they have rebuilt into a landsailer.
Dirk and Al are next shown at a gas station in the middle of nowhere. They call Admiral Sandecker who tells them how important it is to shut down the solar incinerator but that he can't offer them any support. Dirk Pitt gives up his treasured confederate gold piece in exchange for the gas station owner's jeep.
Dirk, Al and the Touareg chief use the car stolen from General Kazim and a disguise to approach the solar incinerator plant and then pull guns on the guards. They find the plant mostly abandoned and decide that Massarde intends to blow the place up. Al goes after the bomb while Dirk goes to save Dr. Rojas. Al nearly gets incinerated and Dirk nearly gets tossed off the central tower, but they are both successful. Massarde gets away in his helicopter.
Dirk, Al and Dr. Rojas take General Kazim's antique car and head for the ruin where they originally hoped to find the CSS Texas. General Kazim then pops up in his helicopter and starts firing on them. They attempt to lose him by throwing the explosives from the solar plant out the back of the car and shooting them to throw up some dust. They then suddenly find the CSS Texas, beached in the desert and run to it for shelter. General Kazim fires on their position while his army approaches on the ground.
Inside the Texas they find lots of gold. However the armor plating on the ironclad turns out to be next to useless against machine guns on General Kazim's helicopter. Then, in the most improbably scene in the movie, our heroes load a 140-year-old shell, into a 140-year-old cannon and use 140-year-old gunpowder to shoot down General Kazim's helicopter. General Kazim's ground troops then surrender in the face of Touareg fighters on the high ground.
After much exposition about how everything has been mopped up, the U.S. Ambassador begs Admiral Sandecker to have NUMA on call to handle special missions that the government might need done. Sandecker doesn't say no. Sequels are set to go.
Massarde is shown dining in an expensive restaurant. His water glass is refilled by a waiter that we recognize as a CIA agent friend of Admiral Sandecker. The agent leaves immediately afterward, and we are left to speculate about the contents of the "water" bottle.
The movie ends with Dirk Pitt and Dr. Eva Rojas canoodling on a beach in California.
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