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As depicted in the film, Colonel Robert Lee Scott, Jr. was determined to fly airplanes, even as a child. In 1921, he bought a WWI "Jenny" at public auction and took flying lessons from a former WWI pilot. Despite his bad academic record, Scott graduated from West Point in 1932, after taking remedial classes. He married his girl friend after a whirlwind courtship and in 1934 became an Army airmail pilot. After war was declared in 1941, Scott applied for combat duty, but was rejected because of his age. He continued to pursue a combat assignment, however, and eventually, after lying about his experience with the Flying Fortress, was given command of one of thirteen bombers assigned to bomb Japan. The proposed bombing was canceled because, in the meantime, the Japanese had taken all American bases in the Philippines. Scott remained in the Far East as a pilot ferrying men, refugees, and supplies along the China-Assam route. Later he convinced General Claire Chennault to give him a P-40 and became an effective combat pilot. Unlike in the film, Scott was never shot down, although his plane was often shot at and he, himself, was wounded. In January 1943, Scott was ordered back to the United States to train fighter pilots.
According to a May 4, 1944 Hollywood Reporter news item, Cary Grant and Humphrey Bogart were both announced as the star of this film. A press release notes that this was at one time to be a Hal B. Wallis production. According to memos included in the records of the War Department, Wallis wanted Colonel Robert L. Scott to play himself in the film, and if that were not possible, wanted Scott to contribute to the script, as he believed the pilot's contribution would make the screenplay more effective. The Army Air Force denied this request, as they believed it would interfere with Scott's military duties. By February 1, 1944, however, Scott was made available for temporary duty as a technical advisor. Other War Department records add that despite objections to an early screenplay, expressed in a September 30, 1943 memo from Colonel William Westlake, assistant to the Director for Army Air Forces, to Allyn Butterfield, Chief of the Feature Film Section of the War Department Bureau of Public Relations, a revised screenplay met with Air Force approval, and by October 1943, War Department cooperation was granted. Macon, GA, the site of the film's world premiere, was Robert Lee Scott's hometown. According to a March 22, 1945 letter from Brig. Gen. Ray L. Owens to Pain, Lowe & Coffin, Esqs. contained in the holdings at NARS, Lieut. Patrick D. Holland was killed during aerial maneuvers that comprised part of his military training and the flight was photographed by the film's cameramen and included in God Is My Co-Pilot. Some scenes were shot on location at Metropolitan Airport in Van Nuys, CA.