The characters were based on people Lawrence Kasdan lived with in the Eugene V. Debs co-op in Ann Arbor, MI, while attending the University of Michigan. Co-ops are co-ed housing in which the residents share household duties like cooking. This explains why the characters are so comfortable sharing the house and cooking, and are so attached to the Michigan football game.
At least twice during the movie we can see an octopus on a TV screen in the house. Of course an octopus has eight legs, and there are eight intertwined friends in the film (counting their friend Alex, who we barely see).
The main house in the film is in Beaufort, SC. It is the same house where The Great Santini (1979) was shot. Director Lawrence Kasdan liked "The Great Santini" so much that he decided to shoot his film in the same house.
Lawrence Kasdan wrote the parts of Karen and Sarah specifically for JoBeth Williams and Glenn Close respectively, however both actresses initially wanted to play the role of Meg as both felt that they better related to that character over the ones chosen by Kasdan.
Meg Kasdan, Jon Kasdan, Jake Kasdan:
Director Lawrence Kasdan's wife Meg plays the airline stewardess flirting with Sam Weber at the beginning of the film. Their son Jon plays Harold & Sarah's son in the bathtub, and their other son Jake plays the boy seeking Sam's autograph at the wake.
As he fights off the bat, Harold hums the theme from Raiders of the Lost Ark (1981), a movie written by Kasdan. Sam Weber's appearance, and career as a television actor, resemble Tom Selleck, who had to turn down the role of Indiana Jones in "Raiders" due to his commitment to Magnum, P.I. (1980).