Plot

In this sexually ambiguous romantic comedy, Luke, a naive college student, struggles with issues of masculinity while he comes to terms with a rare genetic disorder that causes the afflicted to switch gender at will.

Luke, a young man insecure about his masculinity, must solve the mystery of his rare genetic condition, Zerophilia, that changes him from male to female anytime he's aroused--which noticeably complicates his love life. Journey with Luke into the wild world of Zerophilia to discover that you can't change your true nature, even if it can change you. A coming-of-age cult classic.—Anonymous

"Zerophilia" is a condition that the movie as well as the International Organization of Zerophiliacs claims affects approximately 1,000 or more people in the world, who have an extra "Z" chromosome. Following their first experience of sexual intercourse, Zerophiliacs begin to change gender whenever they are sexually aroused. Luke (Taylor Handley), a young man who is somewhat insecure about his masculinity, begins to exhibit Zerophilia following a sexual encounter with a woman (Kelly LeBrock). He meets Michelle (Rebecca Mozo) and experiences partial transformations when they go out together.

He confides about his partial transformations to his best friend Keenan (Dustin Seavey), who contacts Dr. Sydney Catchadourian (Gina Bellman). Dr. Catchadourian persuades Luke to go through a full transformation. Luke accomplishes this through masturbation and becomes "Luca." Luca has difficulty achieving an orgasm to change back, even with coaching from Keenan's girlfriend Janine (Alison Folland). However, a visit by Michelle's attractive brother, Max (Kyle Schmid), who flirts with "Luke's cousin", enables her to get sufficiently aroused to complete the transformation back into Luke.

Luke is threatened by his gender transformation and the questions of sexuality it raises; he seeks help from Sydney. She tells him that a Zerophiliac can become "a-morphic" and stop changing gender only by having sex with another Zerophiliac... such as herself. He relents, but discovers afterward that she wasn't telling him the full truth: an a-morphic Zerophiliac can still change by having sex with another Zerophiliac; Dr. Catchadourian was only using him to change herself into a man, leaving Luke as a woman, Luca.

Comic tensions arise from Luke's efforts to keep Michelle at a distance, Max's defensiveness about his sister, Luca's half-hearted resistance to Max's affections and Luke's confused aggression toward Max. When Michelle discovers that Luke had sex with Dr. Catchadourian, she feels betrayed. Hoping to find Michelle, Luca seeks out Max and reveals the depth of her/(his) affection for Michelle and how sorry he is to have betrayed her. Max is touched by her apology, and reveals that he is actually Michelle. They make love...repeatedly, both changing gender, destined to live happily ever-after alternately as Luca and Max and Luke and Michelle.