McCay had a reputation for his proficient drawing skills, best remembered in the elaborate cartooning of the children's comic strip Little Nemo in Slumberland he began in 1905.

He delved into the emerging art of animation with the film Little Nemo (1911), and followed its success by adapting an episode of his comic strip Dream of the Rarebit Fiend into How a Mosquito Operates.

[4] McCay used minimal backgrounds[5] and capitalized on strengths of the film medium, then in its infancy, by focusing on the physical, visual action of the characters.

[18] Inspired by flip books his son Robert brought home,[19] McCay said he "came to see the possibility of making moving pictures"[20] of his cartoons.

[23] McCay took the idea for the film from a June 5, 1909, episode of his comic strip Dream of the Rarebit Fiend,[24] in which a mosquito (without top hat or briefcase) gorges itself on an alcoholic until it becomes so bloated and drunk that it cannot fly away.

[5] Thus, on each drawing McCay had to redraw the background, which appears to waver slightly due to the difficulty of reproducing it perfectly each time.

It disappeared, and a few days later the police found the abandoned taxi with the drawings unharmed inside, the horses two to three miles away.

The first attempt to shoot the artwork resulted in unacceptable amounts of flicker due to the arc lighting the studio used, and it was re-shot.

[32] In a lost live-action prologue, McCay and his daughter, "pestered to death by mosquitoes" at their summer home in New Jersey, find a professor who speaks the insects' language.

[35] The New York Morning Telegraph remarked that "[McCay's] moving pictures of his drawings have caused even film magnates to marvel at their cleverness and humor".

[35] Audiences found his animation so lifelike that they suggested he had traced the characters from photographs[36] or resorting to tricks using wires:[37] I drew a great ridiculous mosquito, pursuing a sleeping man, peeking through a keyhole and pouncing on him over the transom.

My audiences were pleased, but declared the mosquito was operated by wires to get the effect before the cameras.To show that he had not used such tricks, McCay chose a creature for his next film that could not have been photographed:[36] a Brontosaurus.

[40] Following Mosquito, animated films tended to be story-based; for decades they rarely drew attention to the technology underlying it, and live-action sequences became infrequent.