Loosely based on the novel Expressway written by Trevor Dudley-Smith under the pseudonym Howard North, the film chronicles the aftermath of a 39-car smash-up in California.

From the beginning, California Highway Patrol sergeant Sam Marcum (Robert Conrad) announces in a voice-over that a 39-car smash-up will be the cause of 62 injured people and fourteen deaths.

Meanwhile, a woman named Erica (Vera Miles) is troubled by a gang of bikers including rebellious Burnsey (Sue Lyon), when she is rescued by young Dale (David Groh).

In other sub-plots, Lee Bassett (Scott Jacoby) becomes a murder suspect when he is forced to pick up a young couple on the run, Penny and Pete (Bonnie Ebsen and George O'Hanlon, Jr.).

43 hours before the accident, Erica meets with her colleague Trudy (Terry Moore) at a sleazy bar, where she is introduced to a free-spirited life style.

Nearby, Sergeant Marcum holds a truck for speeding, driven by Randy (Barry Hamilton), and issues a warning to the owner, who is in the back having intercourse with a woman (Cindy Daly).

Medical school drop-out and truck driver Dale witnesses the situation and starts a fight, which lasts until the bikers hear police sirens.

The smash-up soon ensues, killing Lee, Penny, Al, and Burnsey's biker boyfriend Andy (Joel Parks), and badly injuring Dale.