An advertising executive finds herself in a small-town jail after being terrorized on a drive from Los Angeles to New York by two hitchhikers who steal her car and leave her unconscious by the roadside. She becomes a fugitive after killing her jailer during a rape attempt and breaking out with one of the hitchhikers who could prove her innocence.

An accidental overdose of gamma radiation causes a mutation in scientist David Banner's DNA: now whenever he becomes angry, he metamorphoses into a seven-foot-tall, 330-pound, mindless muscular green creature.