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Abby Houston, a successful author, waltzes into the small town of Bliss, Mississippi. Abby's used to making up quirky, charming characters in her books, but here in Bliss it almost seems like those characters have sprung to life and Abby is fantasizing about moving right in.

In 1977, college graduates Harry Burns and Sally Albright share a contentious car ride from Chicago to New York, during which they argue about whether men and women can ever truly be strictly platonic friends. Ten years later, Harry and Sally meet again at a bookstore, and in the company of their respective best friends, Jess and Marie, attempt to stay friends without sex becoming an issue between them.