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The Killer Shrews was the first of three productions by Hollywood Pictures Corp. and financial backer and executive producer Gordon McLendon. Along with the other two films, The Giant Gila Monster and My Dog Buddy ( and below), The Killer Shrews was shot in Dallas, TX. A December 1959 Los Angeles Times review of the film stated there was no screenplay or director's credit on the film that the reviewer watched, but those credits, as listed above, were on the print viewed. Although the credits in publicity materials and the Variety review list the character played by Ken Curtis as "Jerry Lacer," he is called "Jerry Farrell" in the film. McLendon was the head of a radio group and president of Tri-State Theatres and co-starred as "Radford Baines."
Although a January 1959 Los Angeles Times article stated that B. R. McLendon, who also financed the picture, would play a role, his appearance in the final film has not been confirmed. Ingrid Goude, who portrayed "Ann Craigis," was a former Miss Sweden. Baruch Lumet, who played "Dr. Marlowe Craigis," was the father of director Sidney Lumet. According to the Variety review, the film cost $123,000 to produce. The picture marked the directorial debut of Ray Kellogg, who served as the head of Twentieth Century-Fox's special effects department throughout most of the 1950s.