Though a childhood bout with polio left him dependent on an iron lung, Mark O'Brien maintains a career as a journalist and poet. A writing assignment dealing with sex and the disabled piques Mark's curiosity, and he decides to investigate the possibility of experiencing sex himself. When his overtures toward a caregiver scare her away, he books an appointment with sex surrogate Cheryl Green to lose his virginity.
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.