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A team of researchers sets off into a jungle in Padrang - Borneo, Indonesia to search for a "blood orchid", a flower they believe can be used as a type of fountain of youth. Though their guide Bill Johnson (Johnny Messner) has misgivings about which path to take, Jack Byron (Matthew Marsden) bribes him to take the path he doesn't think is safe. The team ends up going over a waterfall and having to wade through the river. A giant anaconda emerges from the water and swallows Dr. Ben Douglas (Nicholas Gonzalez) whole, while the rest of the team escapes the river. Bill tries to assure them that it was the largest snake he's ever seen and that it should take weeks' for it to grow hungry again, however most of the team demands that the expedition be called off.
They decide to travel to Bill's friend John Livingston (Andy Anderson) who lives on the river to see if he can borrow his boat and his whale. While traveling to the boat, Bill tells Sam (KaDee Strickland) about Jack bribing him into taking the unsafe route. Along the way, Bill finds an infestation of leeches on Cole's (Eugene Byrd) back and burns all of them with his lighter while Tran (Karl Yune) finds a poisonous spider in Gordon Mitchell's (Morris Chestnut) shoe. Jack decides to take the spider along for further study and then everyone resumes the journey to the boat.
However, Livingston is killed by another anaconda and his boat crashes into the riverbank. The team sees an explosion and finds the boat wrecked and are disappointed for losing their chance for escape from the jungle and find only a few essentials for their quest. While continuing their journey, they find Livingston's chewed up corpse. Bill realizes that it must be mating season, which means all of the male anacondas come out of their territories to find the nearest female in its mating pit.
They find themselves in a small native village consisting of thatched huts where a disemboweled anaconda with a pair of human legs hanging out of the snake's abdomen is displayed. The team speculates that the snakes are unusually large in size because their lives have been extended through the orchids, which are a part of the local food chain. Jack says that since they must be close to the orchids, they should press on. However the others contend that there is no evidence that the orchids will have the same effect on humans and still want to leave, so they start building an escape raft.
Meanwhile, Gordon discovers that Jack had secretly obtained Livingston's private case containing a radio and a gun and realizes he could have called for help long ago. When Jack is unable to convince him to allow the expedition to continue, he paralyzes him using the spider. As Jack joins the others at the raft, Sam discovers a paralyzed Gordon and notices the spider bite on his arm. While Sam was interrogating Jack about what he had done to Gordon, an anaconda drops down from the rafters and swallows Gordon alive soon after she leaves the building. The others arrive just as it finishes, so Bill sets the building on fire. Jack uses the commotion to steal the raft.
With no more material to make another raft, they decide to bushwack through the jungle to beat Jack to the orchids and get back their raft. On the way they fall into a cave trying to escape an anaconda. Cole gets lost and panics after finding a skeleton. He runs into Tran. Together they make their way back to the others. Along the way, Tran falls through a hole in the cave floor. Unable to escape, he is eaten by an anaconda underwater. The terrified Cole manage to make their way back to the team, escaping the caves behind them seconds ahead of the snake. It follows them through the hole, and attacks them. Sam uses a machete to behead the snake, but Cole is captured by another giant anaconda. The team follows and find him being constricted, but still alive. Bill throws his knife and impales the snake through the head, killing it and freeing Cole.
The group finds the raft just as Jack finds the blood orchids, hanging precariously above a pit in which a ball of male anacondas are mating with the female. Jack shoots Bill in the arm, and forces the party to accompany him to the orchids. He has Sam cross the pit via a thin log to fill a backpack with orchids. As she makes her way back, the log starts to crack. Jack orders her to throw him the backpack, but Sam counters to threaten to drop the flowers into the pit unless he drops the gun. The log breaks and she falls, landing halfway down the pit. As the others help her climb out, Jack tries to get the backpack. The spider he used to paralyze Gordon escapes its jar and bites him. Jack falls into the pit and is devoured, as Sam and the others escape.
The female anaconda notices them, but Gail (Salli Richardson) tricks it into biting their fuel container. Bill tries to shoot the container, but the gun is empty. Cole shoots it with a flare, causing a chain reaction that kills the snakes, along with all the blood orchids as well. Bill, Sam, Cole, Gail, and Bill's pet monkey Kong make it back to the raft and leave. As they set off with their raft, Bill suggests another shortcut, but the others suggest that they won't take the shortcut.
Cast
Johnny Messner as Bill Johnson
KaDee Strickland as Sam Rogers
Matthew Marsden as Dr. Jack Byron
Salli Richardson as Gail Stern
Eugene Byrd as Cole Burris
Nicholas Gonzalez as Dr. Ben Douglas
Karl Yune as Tran Wu
Morris Chestnut as Gordon Mitchell
Denis Arndt as CEO
Andy Anderson as John Livingston
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