The novel grew out of a short story, "Intergalactic P.S. 3", first published as a pamphlet for Children's Book Week in 1970. In this early version of the narrative, Mrs Whatsit, Mrs Who and Mrs Which from A Wrinkle in Time send Charles Wallace, Meg and Calvin to a school on another planet, where Proginoskes and a conifer seed version of Sporos are among their classmates. As in the novel, Meg must identify the real Mr. Jenkins among his two impostors. If she fails, it will be "a victory for the Dark Shadow" (i.e. the Black Thing).
In Walking on Water: Reflections on Faith and Art, L'Engle states that at one stage in the writing of A Wind in the Door, she knew who most of the characters would be, including Progo, the snake and "the three Mr. Jenkinses." She had difficulty developing the story, however, until a physician friend gave her two articles about mitochondria. "And there was where the story wanted me to go," L'Engle writes, "away from the macrocosm and into the microcosm." Enlisting the help of her elder daughter, she proceeded to give herself "a crash course in cellular biology," which she found to be hard work, but also a lot of fun.