Harman and Ising had long aspired to start their own studio, and had created and copyrighted the cartoon character Bosko in 1928. After losing their jobs at the Winkler studio, Harman and Ising financed a short Bosko demonstration film called Bosko, the Talk-Ink Kid. The cartoon featured Bosko at odds with his animator – portrayed in live-action by Rudy Ising; impressed Leon Schlesinger, who paired Harman and Ising with Warner Bros. Schlesinger wanted the Bosko character to star in a new series of cartoons he dubbed Looney Tunes (the title being a parody of Walt Disney's Silly Symphonies). The pair made Sinkin' in the Bathtub in 1930, and the cartoon did well. Harman took over direction of the Looney Tunes starring the character, while Ising took a sister series called Merrie Melodies.
The two animators broke off ties with Schlesinger later in 1933 over budget disputes with the producer, and went to the Van Beuren studio, which was making cartoons for RKO Radio Pictures. There, they were offered a contract to produce the Cubby Bear cartoon series. Harman and Ising produced two released cartoons for this series, but were in the midst of making a third cartoon when a contractual dispute arose. The pair left Van Beuren, but kept the completed cartoon and finally released it in the 1940s.
Harman and Ising had maintained the rights to the Bosko character, and they signed a deal with Metro-Goldwyn-Mayer to start a new series of Bosko shorts in 1934. The two maintained the same division of work they had used at Warner Bros.: Harman worked on Bosko shorts, and Ising directed one-shots. They also tried unsuccessfully to create new cartoon stars for their new distributors. Their cartoons, though technically superior to those they had made for Schlesinger at Warner's, were still music-driven shorts with little to no plot. When the new Happy Harmonies series ran significantly over-budget in 1937, MGM fired Harman and Ising and established its own in-house studio, the Metro-Goldwyn-Mayer cartoon studio.
Harman and Ising still found work at the time as animation freelancers. Harman and Ising lent their former ink-and-painters to Walt Disney while Snow White and the Seven Dwarfs was behind schedule. Disney afterward commissioned Harman and Ising to produce a Silly Symphony cartoon, Merbabies, in return. Disney reneged on a deal he had made for two other Harman-Ising cartoons to be produced for the studio. Harman and Ising sold the cartoons to MGM, and Quimby later agreed to hire the animators at MGM's cartoon studio.