NASA needed to transport outsize cargo from manufacturing plants such as the Michoud Assembly Facility in New Orleans, Louisiana, to Cape Canaveral Air Force Station in Florida.

John M. "Jack" Conroy, a retired United States Air Force pilot, and Lee Mansdorf, an aircraft salesman and entrepreneur, formulated the Guppy concept one evening over dinner.

[1] NASA's Project Gemini made early use of the Pregnant Guppy to transport the first and second stages of Titan II GLV from the Martin Co. in Baltimore, Maryland, to Cape Canaveral, Florida.

[citation needed] Aero Spacelines was sold in August 1965 to Unexcelled, Inc., a publicly-traded company that had subsidiaries engaged in discount store retailing, meatpacking equipment and iron castings.

[8] In November 2019, NASA used the aircraft to transport the Orion capsule from the Kennedy Space Center to the Mansfield Lahm Airport in Ohio for thermal and vacuum tests.