In the morning, Old Bull Lee, Sal, and Dean attempt to pull nails out of an old piece of wood. This gives Bull time to talk about his theories of government conspiracy, his crazy relatives, and his invention for warding off cancer. In the afternoon Bull and Sal go to a "bookie joint" to gamble, where Sal has a vision in which a racing horse reminds him of his father. On the way home, Bull tells Sal that he believes mankind will soon realize they can talk to the dead.
Back at Bull's house, the travelers compete in athletic competitions like running and jumping, and Dean wins them all. After an afternoon in New Orleans where Dean shows Sal the ins and outs of the rail yard, the group say farewell to the Lees and leave New Orleans. Sal muses about the feeling of seeing someone become smaller as you drive away until they are just specks on the horizon.
They stop at a filling station and steal more food, gas, and cigarettes because they only have just enough money to get to San Francisco. As they enter the swamps of Louisiana, they become frightened and awed by the night and the wild forest surrounding them. Exiting the swamp, they can see the oil tanks and refineries of Texas. They enter Houston, and Dean tells stories of his Houston days with Bull Lee and Carlo Marx. Sal takes over driving through Texas in the rain and gets the car stuck in mud after a car full of drunk field workers runs them off the road. The next day there is snow on the ground, and Marylou tempts Sal with promises of a relationship in San Francisco. They drive all the way to El Paso, stopping only once for Dean to take off all his clothes and run through the fields of sagebrush. Dean convinces Sal and Marylou to take off their clothes as well, and they all sit in the front seat together and drive on.
In El Paso Dean takes off to "dig the streets" and leaves Sal and Marylou alone in the car. She tries again to come on to him, but he wants to wait until Frisco. Marylou confesses her confusion over her love for Dean and how she is sure he is going to leave her. Dean picks up a hitchhiker, and they decide to go to Tucson, Arizona, where a friend of Sal's owes him five dollars.
In Arizona Sal pawns his pocket watch for a dollar of gas money, and a cop stops them to check their papers. Dean comments that the cops are always skeptical of groups of young people who come into town and start pawning their possessions. In Tucson they meet up with Sal's friend Hingham, a writer, who gives Sal five dollars and feeds the group. As they leave Hingham, Sal again thinks about watching his friends become smaller as they drive away.
They pick up another hitchhiker, a musician, who promises them money in Bakersfield. They roll into California, and Dean tells stories about his days in Bakersfield. The hitchhiker finds his brother in Bakersfield and gives the group money for gas. They drive the rest of the way to San Francisco, where Sal and Marylou get stranded on the street with no money for a hotel room while Dean makes arrangements with Camille.
Having been abandoned by Dean, Sal and Marylou get a hotel room on credit and scrounge for food. Sal realizes Marylou has no real feelings for him and was only trying to get to Dean through him. As they lie in bed at night, and Sal tells myths of God and Satan that he has conjured up. When Marylou leaves him for a club owner, Sal wanders the streets of San Francisco, where he has visions of his past and of reincarnation.
Dean, who has taken a job as a door-to-door salesman, finally takes Sal back in. After a few days of selling steam cookers, Dean and Sal become tired of life and Dean quits his job. They become "mad" again, however, when they go to a show by a jazz musician/performance artist named Slim Gaillard. Later, Sal and Dean experience the "madness" of African American jazz all over the Bay area. Sal finally becomes overwhelmed and tired by the scene and catches a bus back to New York, "thinking we'd never see one another again and we didn't care."
The continuing trip to San Francisco gives Sal time to think about the transitory nature of life. Watching his friends fade away in the rear window of a car makes Sal realize the flow of time and the process of continual loss. It is a feeling that Sal finds both futile and liberating. For Dean, it becomes a necessity to retell the stories of his past as they drive through the towns of Texas and into California. The stories are often amoral and shocking, especially when the reader keeps in mind the cultural sensibilities of the 1950s when On the Road was published. These stories are Dean's own way of dealing with the idea of impermanence.
The group's journey through the Louisiana swamps is again a way in which Kerouac mythologizes black culture in America. The group longs to find a jazz club in the swamp to experience this culture, but they end up being just as frightened of the swamp as they are excited by it. As Sal, Dean, and Marylou continue to drive west (Ed and Galatea Dunkel have disappeared from the narrative, apparently staying in New Orleans), Dean's behavior becomes even more erratic, driving naked and talking nonsense.
Once they reach San Francisco, Sal and Marylou find the town not as exciting or accommodating as they had hoped. They end up being left broke and homeless as Dean abandons them for other adventures. Unlike his earlier experience, Sal now only sees the "disenchanted" and sad side of San Francisco.
Hungry and abandoned in San Francisco, Sal has a vision on the streets that begins to grasp the truth he has been searching for in his journeys. In this vision of reincarnation and divinity, Sal begins to see the fluidity, not permanence, of time. Many of the themes of this passage use Buddhist notions, ideas that would gain more importance in Kerouac's later work. Throughout the novel, Sal's character has been increasingly fluid in his identity: he has been a hobo, a traveler, a prophet, a family member, and so on. It is in this passage of visions that Sal begins to grasp the notion of his identity as being truly fluid.
In the final chapter of this second part, Dean takes Sal back in, but Dean's character has also changed. No longer a wild, amoral youth of the road, Dean has come back to San Francisco to provide for a family, take a job, and become stable. Yet, this new role for Dean cannot last long, and it is only a few days later that Sal and Dean lie around Dean's house, "sick and tired of everything."
It is, again, the underground jazz of African American culture that drives Sal and Dean "mad" again and renews their faith in life. Kerouac's prose takes on the unresolved, confused nature of the music itself as he attempts to describe several of these African American characters and the madness that they bring with them. After an exhausting night out in which Dean, Marylou, and Sal "hit ... the Negro jazz shacks," Sal decides to head back east. Sal is now burned out by the frantic pace of his travels.