An American submarine leaves Tierra Del Fuego, and one of its crew has secretly brought aboard a container full of poisonous snakes which escape storage and bite key personnel on the submarine, causing an accident that cripples the vehicle so that it drops to the bottom of the Southern Ocean. Worse still, the snakes are still at large on the submarine and complicate the efforts of the crew to escape the sunken vessel.

FBI agent Neville Flynn boards a flight from Honolulu, Hawaii to Los Angeles, escorting a key witness to testify against a mob boss at an upcoming trial. An on-board assassin releases a crate full of hundreds of deadly venomous snakes in an attempt to eliminate the witness. Flynn and a host of frightened passengers and crew must band together to survive the slithery threat.