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The working titles of the film were The Box Step and The Best of Friends. The full onscreen copyright statement listing the film's claimants reads; Filmways, Inc., Raymax Productions, Inc., Raven Productions, Inc. & Virgo International Pictures, Inc. Before the opening credits roll, a series of Hearst Metrotone Newsreels depicting Franklin and Eleanor Roosevelt and the fictional Hill-Bruckner trial are shown.
Many reviews commented on the similarity between What's the Matter with Helen? and the 1962 Robert Aldrich film What Ever Happened to Baby Jane?. Henry Farrell, who wrote the script for What's the Matter with Helen?, wrote the novel on which What Ever Happened to Baby Jane? was based. According to a January 1971 article in Los Angeles Times and a December 1970 Variety news item, director Curtis Harrington and producer George Edwards, who at the time were working for Universal Pictures, were so impressed by What Ever Happened to Baby Jane? that they asked Farrell if he had any other properties available. Farrell was at the time working on a story called "The Box Step," a contemporary story about two ladies who ran a dance school, but it had already been optioned by Farrell's agent. The property was assigned to another director at Universal, and Farrell was commissioned to write the screenplay.
Universal eventually decided to abandon the property and asked Harrington and Edwards if they still wanted it. At that time, Harrington and Edwards changed the period to the 1930s and offered the lead to Joanne Woodward, who turned it down. Months later, after leaving Universal, Harrington and Edwards took the project to Edward S. Feldman at Filmways, who was looking for a script for Debbie Reynolds. According to Filmfacts, Reynolds invested $800,000 in the production. A September 1969 Daily Variety news item added that the producers were negotiating with Estelle Parsons to star in the film. The Los Angeles Times article added that Winters was threatened with the replacement of Geraldine Page if she did not become easier to work with. According to a January 1971 Hollywood Reporter news item, the scenes depicting the Kansas farm were shot on location in the Palos Verdes area of California. The film received an Academy Award nomination for Best Costume Design. A few months after completing What's the Matter with Helen?, Harrington directed another film starring Winters, Who Slew Auntie Roo?, which was shot in England and released in December 1971 (see below).