"Little Girl in the Big Ten" was written by producer Jon Vitti and directed by Lauren MacMullan. The idea for the episode was pitched by Vitti, who suggested an episode in which Lisa meets girls who thought she was a college student. It was first broadcast on the Fox network in the United States on May 12, 2002. Jean thought the idea was "brilliant", and the subplot involving Bart in a "germ-free" plastic bubble was conceived by the writers wanting to make "the most different subplot from[...] an intellectual college plot" they could think of. A scene in the episode shows Lisa talking to Bart on the branch of a tree in their garden. Bart says the line "You can't believe what that sunset looks like to me", to which Lisa replies "That's not a sunset, that's a bird on fire." Originally, Lisa's line read "[...] that's a plane on fire," however, after the September 11 attacks, the line was considered offensive and was changed. "[...] since we work so far ahead we usually do these things that are sort of timeless stories," Jean said, "but every once in a while there's something that turns out to be ironic in a bad way, then we have to change it."