While practicing motocross in Hawaii, Sean Jones witnesses the brutal murder of an important American prosecutor by the powerful mobster Eddie Kim. FBI agent Neville Flynn persuades him to testify against Eddie in Los Angeles. They board the red-eye Flight 121 of Pacific Air, occupying the entire first-class section. However, Eddie dispatches hundred of different species of snakes airborne with a time-operated device in the luggage to release the snakes into the flight with the intent of crashing the plane. Neville and the passengers must struggle with the snakes to survive.