Sal, Dean and Marylou drive through Louisiana and Texas, stealing food, cigarettes and gas when they can. They see a huge fire in the night, and scare themselves by driving slowly with the headlights off in a swampy forest. Later, in pouring rain, Sal driving, they are forced onto the side of the road by a car driving straight at them. The offending car is full of drunk fieldworkers who want to ask directions. Sal points the way, then realizes that their car is stuck in the mud. He wakes Dean up, and they push it out and continue on, wet and covered with mud. In the day, they pass through snowy ranges and plains. Once, Dean stops and runs around naked in the sagebrush. He persuades Sal and Marylou to strip as well, and they drive along naked for awhile, shocking passing truckdrivers.
At dark, they stop at the El Paso travel bureau, hoping to find ride-sharers to chip in for gas, but with no success. Sal observes Marylou watching Dean with sadness, anger and love. They drive again, and pick up a quiet boy who promises them money from his aunt in California. They continue on through the purple and red mountains of New Mexico, and then Arizona. Sal, who has taken over driving for awhile, stops to pawn his watch, and they are stopped by another suspicious policeman--but the policeman is amused by Dean and lets them go. In Tucson, they stop briefly at Sal's friend Hingham's house to borrow five dollars.
They pick up another hitchhiker: an "Okie" musician whose guitar has been stolen; he promises them gas money from his brother in Bakersfield. As they pass a women's prison, he tells them a story about a man who was shot by his wife, forgave her, and bailed her out of prison, only to be shot again. They pass through a high mountain pass; on the way down, Dean negotiates the curves in neutral--instructing the others which way to lean--and they make it thirty miles without using gas.
In Bakersfield, Dean is overwhelmed by memories, telling Sal details of his old hangouts. Sal tries to tell Dean about being in the railyard with Terry, but Dean is too excited to listen. They get a few dollars from the musician's brother, and continue on to the aunt in California. But--coincidentally enough--the boy's aunt has gone to jail for shooting her husband. They wish the boy well and go on, soon seeing hilly, beautiful San Francisco, and the ocean beyond. After arriving downtown, Dean leaves Sal and Marylou in the street and rushes off to Camille.
Marylou and Sal stay in a cheap hotel. Without Dean there, Sal realizes that Marylou has no interest in him. She goes off with a wealthy man the second night. Walking through the city alone, Sal experiences a strange moment in which he imagines a store proprietess to be his disapproving mother from a past life. He feels a roar in his ears and thinks he feels the presence of numerous past lives, a sensation of bliss and imminent death--but he makes it back to his room, where he feels ravenous and describes at length the delectable smells of food in San Francisco.
Dean comes back, and takes Sal to Camille's for a few days. Dean has a new scheme: selling pressure cookers. Predictably, this doesn't last very long. Sal and Dean go out with Slim Gaillard, going to long, passionate jazz and blues sessions. Sal prepares to go home. Dean is back with Marylou again; Sal is sick of them. The three part, feeling slightly hostile towards each other.