Main Street, the story of an idealistic young woman's attempts to reform her small town, brought Lewis immediate acclaim when it was published in 1920. It remains one of the essential texts of the American scene. Lewis Mumford observed: "In Main Street an American had at last written of our life with something of the intellectual rigor and critical detachment that had seemed so cruel and unjustified [in Charles Dickens and Matthew Arnold]. Young people had grown up in this environment, suffocated, stultified, helpless, but unable to find any reason for their spiritual discomfort. Mr. Lewis released them."

Carol Milford, the daughter of a judge, grew up in Mankato, Minnesota, and became an orphan in her teens. In college, she reads a book on village improvement in a sociology class and begins to dream of redesigning villages and towns. After college, she attends a library school in Chicago and is exposed to radical ideas and lifestyles. She becomes a librarian in Saint Paul, Minnesota, the state capital, but finds the work unrewarding. She marries Will Kennicott, a doctor, who is a small-town boy at heart.

When they marry, Will convinces her to live in his home-town of Gopher Prairie, Minnesota, a town modeled on Sauk Centre, Minnesota, the author's birthplace. Carol immediately sets about her plans to remake Gopher Prairie. But she is filled with disdain for the town's physical ugliness and smug conservatism.

She speaks with its members about progressive changes, joins women's clubs, distributes literature, and holds a party to liven up Gopher Prairie's inhabitants. Despite her ineffective efforts, she is constantly derided by the leading cliques.

She finds comfort and companionship with a variety of social outsiders in the town, but these companions all fail to live up to her expectations.

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