Jules Feiffer's original play only lasted on Broadway for 7 performances in 1967. It did however enjoy a more successful run in London with the Royal Shakespeare Company the following year which prompted a revival on Broadway in 1969. This proved to be much more popular, running for 400 performances.
Jean-Luc Godard was courted to direct but he refused to attend any meetings. His reason why was "When my wife and children ask me to tell them that I love them, I tell them to go fuck themselves". (A typically elliptical quote from Godard who doesn't have any children.)
Alan Arkin had directed the play in its Off-Broadway production in 1969 so was one of the more natural choices to direct the film version. (The 1967 Broadway production was directed by George L. Sherman.) Other people involved in Arkin's 1969 production who subsequently worked on the film were Vincent Gardenia, Jon Korkes, and Elizabeth Wilson.
Co-stars John Randolph and Doris Roberts also would later appear together in 1989's National Lampoon's Christmas Vacation as character's Clark and Ellen Griswolds' (Chevy Chase and Beverly D'Angelo) in-laws.
Star Elliott Gould starred in the original 1967 Broadway production of "Little Murders", which flopped after one week of seven performances in late April at the Broadhurst Theatre. Gould was the only cast member to appear in the film, reprising his role as Alfred Chamberlain. The Broadway cast included Barbara Cook as Alfred's girlfriend and future wife Patsy Newquist, Heywood Hale Broun as her father Carol Newquist, Ruth White as her mother Marjorie, and David Steinberg as her brother Kenny. Phil Leeds appeared as Lt. Practice and Richard Schaal was Rev. Dupas. Alfred's parents did not appear as characters in the original play.