In the winter of 1947, the reckless and joyous Dean Moriarty, fresh out of another stint in jail and newly married, comes to New York City and meets Sal Paradise, a young writer with an intellectual group of friends, among them the poet Carlo Marx. Dean fascinates Sal, and their friendship begins three years of restless journeys back and forth across the country. With a combination of bus rides and adventurous hitchhiking escapades, Sal goes to his much-dreamed-of west to join Dean and more friends in Denver, and then continues west by himself, working as a fieldworker in California for awhile, among other things. The next year, Dean comes east to Sal again, foiling Sal's stable life once more, and they drive west together, with more crazy adventures on the way at Bull Lee's in New Orleans, ending in San Francisco this time. The winter after that, Sal goes to Dean, and they blaze across the country together in friendly fashion, and Dean settles in New York for awhile. In the spring, Sal goes to Denver alone, but Dean soon joins him and they go south all the way to Mexico City this time.

Through all of this constant movement, there is an array of colorful characters, shifting landscapes, dramas, and personal development. Dean, a big womanizer, will have three wives and four children in the course of these three years. Perceptive Sal, who at the beginning is weakened and depressed, gains in joy and confidence and finds love at the end. At first Sal is intrigued by Dean because Dean seems to have the active, impulsive passion that Sal lacks, but they turn out to have a lot more in common. The story is in the details.

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