While conducting a research experiment intended to bring about an alternative to modern surgery, exhausted Los Angeles surgeon Dr. Daniel Jekyll falls asleep and accidentally inhales the white powders, transforming him into a wildly uninhibited nymphomaniac.

Wendell Lawson has only six months to live. Not wanting to endure his last few months of life waiting for the end, he decides to take matters into his own hands and enlists the help of a delusional mental patient to help him commit suicide.

Orphaned and left in the desert as an infant, Evil Roy Slade grew up alone—save for his teddy bear—and mean. As an adult, he is notorious for being the "meanest villain in the West"—so he's thrown for quite a loop when he falls for sweet schoolteacher Betsy Potter. There's also Nelson L. Stool, a railroad tycoon, who, along with his dimwitted nephew Clifford (Henry Gibson), is trying to get revenge on Evil Roy Slade for robbing him.

When an upwardly mobile couple find themselves unemployed and in debt, they turn to armed robbery in desperation.

The Bandit goes on another cross-country run, transporting an elephant from Florida to Texas. And, once again, Sheriff Buford T. Justice is on his tail.