Anthropologist Steve Cale is leading director Terri Flores and her film crew down a river to small Indian village where they will shoot a documentary on the mysterious tribe. After rescuing a strange character, Paul Sarone, from his sinking boat, they continue on their search for the tribe. But Sarone's motives are to try to find the great Anaconda inhabitating the river, and when Cale suddenly falls ill from an insect bite, Sarone takes the boat over and leads them into a perilous journey of life and death with the largest snake of their lives.

The cast includes: Jon Voight, Ice Cube, Jennifer Lopez, Eric Stoltz, Owen Wilson, Kari Wuhrer, Danny Trejo, and Frank Welker, Johnathan Hyde, and Vincent Castellanos.

Directed by: Luis Llosa.