Sissy Hankshaw, the novel's protagonist, is a woman born with enormously large thumbs who considers her mutation a gift. The novel covers various topics, including free love, drug use, birds, political rebellion, animal rights, body odor, religion, and yams.
Sissy capitalizes on the size of her thumbs by becoming a hitchhiker and subsequently travels to New York, United States (U.S.). The character becomes a model for The Countess, a male homosexual tycoon of feminine hygiene products. The Tycoon introduces Sissy to a staid Mohawk named Julian Gitche, whom she later marries.
In her later travels, she encounters, among many others, a sexually open cowgirl named Bonanza Jellybean and an itinerant escapee from a Japanese internment camp happily mislabeled The Chink. The Chink is presented as a hermetic mystic and, at one point. writes on a cave wall, "I believe in everything; nothing is sacred. I believe in nothing; everything is sacred," and frequently says, "Ha Ha Ho Ho and Hee Hee."
A flock of whooping cranes also makes frequent appearances throughout the novel, which includes details of their physical characteristics and migratory patterns. Robbins also inserts himself into the novel (as a character).