After their stay in New York City, the Pranksters head to upstate New York to the compound of Timothy Leary and his disciples. Leary is a fellow advocate of acid use, a former Harvard professor who was kicked out of the school. Leary and his disciples eventually landed in Millbrook, New York, at a private estate where they are conducting their own experiments with LSD and Eastern religion.
The Pranksters expect to be greeted warmly by Leary's group as brothers and sisters who are also on a journey of discovery, but instead Leary's group is "cold" towards them. They begrudgingly invite the Pranksters to stay and take them on a tour of their compound, but Babbs, put off by the cold welcome they received, takes over the tour and begins mocking Leary's group and their insistence on merging their acid trips with Buddhism. He makes fun of their meditation rooms, calling them the "crypt trips," and the Learyites are not amused. The Pranksters, put off by Leary's group's refusal to have fun with them - and Leary's refusal to even meet with the Pranksters while he is on "a very serious experiment, a three day trip" on acid - decide to leave New York.
The group begins their journey back home, and all take turns driving, this time taking a Northern route across the U.S. to get back to California. Sandy, who took a new form of acid called DMT when he was in New York, becomes increasingly paranoid. He is not able to come down from his trip, an experience that he equates with getting on and off the bus. The group goes into Canada for the "Calgary Stampede," and one of the Pranksters comes back to the bus with a young girl whom the group names "Anonymous." The Canadian Royal Mounties come to the bus looking for the girl (she was a runaway), but she looks so strange that she blends right in with the group and the Mounties don't know who she is.
In Boise, Idaho, the Pranksters "cut through" a funeral, and a little boy starts to run after the funny-looking bus. They speed up and slow down, teasing the boy for eight blocks, never letting him quite catch up, until they finally gain speed and roar out of town. The Pranksters see this is an "allegory of life...[and] of the multitudes who very shortly will want to get on the bus...themselves."
Back in La Honda, Sandy can't quite shake the delusions that have been plaguing him since New York. For Sandy, "the bus had stopped but he hadn't." He grows steadily more paranoid and begins to believe that the rest of the Pranksters are planning to trick him. He keeps a suspicious eye on the rest of the group, never quite joining them for activities, and Kesey grows angry and worried. The group plans a big game in which they each have to accomplish "tasks" for each other. Sometimes the tasks are big, like dividing up everybody's things into communal property, and sometimes they are small, like starting a fire in the yard. Sandy, paranoid that the tasks are part of a prank, refuses to complete his assignment. Kesey takes a special interest in him then, and all the Pranksters make an effort to give Sandy more positive attention to help him emerge from his problematic state. Sandy, however, views everything they do as a malicious act.
The group takes a trip to a resort called the Esalen Institute, where Kesey is slated to teach a seminar. The Esalen Institute, run by a man named Fritz Perls, is "a place where educated middle-class adults came in the summer to try to get out of The Rut and wiggle their fannies a bit." At the resort, the Pranksters try again to give Sandy positive attention and get him to live in the "Now." One night, the group tries to take him on a procession, a "ceremony of love," to the seashore, but as the group is winding down the steep cliffs towards the beach, Sandy begins to think that the group is ganging up on him. He takes off, running away down the coast, and starts knocking on the doors of the expensive vacation houses in Big Sur until the police pick him up and take him to jail. Sandy's brother, Chris, flies in from New York to bail him out, and Chris takes Sandy back to New York to get him the help that he needs.
The Pranksters' trip to New York to visit Timothy Leary doesn't go as planned. It is clear that the hippie movement is progressing along several divergent pathways. Leary's group is focused on molding their LSD trips around established religious experiences, while Kesey's group is far more freewheeling and fun-loving.
In later interviews, Wolfe said that one of the reasons he wanted to write about the Pranksters was that he felt their group had the makings of a new religious phenomenon: a dynamic leader and "rituals" based around transcendent experiences. However, it is clear from the group's cross-country trip that their erratic behavior is oftentimes as much of a hindrance to their transcendent experiences as it is a help. Leary's group takes their drug experiences much more seriously, modeling them around established religious traditions. For Kesey, the LSD experience is a much more democratic affair, bringing people together and helping them to transcend the world around them. Kesey critiques the Learyites by placing them in a long tradition of "New York intellectuals" whose only goal is to find "another country, a fatherland of the mind, where it is all better and more philosophic and purer, gadget-free, and simpler and pedigreed: France or England." The Pranksters see the Learyites as replacing France and England with the Far East, and as replacing intellectualism with Eastern religion and LSD. Kesey believes that those were never the true paths to transcendence. Their trip East is a kind of metaphor: the goal of the Beat Generation was always to move West, into the great American frontier. The Pranksters are the result of this movement, and now they are heading back East - a different breed of counter-culture altogether.
Kesey and the Pranksters are not wholly separated from the academic world. Kesey has always been tied to his back-country roots, and the Pranksters are an amalgamation of low- and middle-class individuals, some educated and some not. The hippie movement, which was historically based in college towns like Berkeley and Cambridge, also frequently found roots in a middle-class, middle-American "type" exemplified by the Pranksters.
Sandy's illness also highlights the dangers inherent in the Pranksters' lifestyle. Their movement East is fraught with little sleep and enormous amounts of drugs. They keep themselves doped up on speed and marijuana, trying to keep themselves simultaneously active and mellow. Sandy is the next Prankster to begin to lose his mind. He compares his trip to being unable to step off of a bus. His insomnia takes over and he becomes very paranoid, unable to communicate or interact with the rest of the Pranksters. Eventually, he runs away, only to be taken into the care of the police and his brother from New York. Again, it is the established authorities of society, represented by the police and the psychiatrists, that act as support nets for Pranksters who fall far enough into insanity that they lose their ability to function.