A mad scientist's DNA experiment on the bones of a mysterious jungle creature brings the carnivorous beast to life, and only his former assistant Ash Mattley and CIA operative Claire Sommers can stop it.

After the 1860s Wild West, a group of misfit settlers - including ex-doctor Phil Taylor, prostitute Belle, and homosexual bookseller Julian - decide they cannot live in their current situation in the west. They hire a grizzled alcoholic wagon master by the name of James Harlow to take them on a journey back to their hometowns in the East.

Tensions run high when a crazed bomber rigs a Los Angeles bus with a device that will kill everyone on board if the vehicle's speed dips below fifty miles per hour.