Raoul Duke and his attorney Dr. Gonzo drive a red convertible across the Mojave desert to Las Vegas with a suitcase full of drugs to cover a motorcycle race. As their consumption of drugs increases at an alarming rate, the stoned duo trash their hotel room and fear legal repercussions. Duke begins to drive back to L.A., but after an odd run-in with a cop, he returns to Sin City and continues his wild drug binge.

A band of satanist hippies roll into a town and begin terrorizing the local folk. After raping a local girl, her grandpa goes after them, only to be beaten and forced to take LSD. His grandson then plots revenge on the satanists by feeding them meat pies infected with blood from a rabid dog. They turn into crazed lunatics and begin killing and/or infecting everything in their path.