Akira Uehara is a gentle, somewhat effeminate high school boy who has developed a crush on his classmate, Nanako Momoi. On the surface, Nanako appears to be a cute girl, but she is notorious for her violent, short-tempered, and overwhelmingly tomboyish personality, which terrifies most of their peers. The story takes place in a contemporary Japanese town, centered around their school and Nanako's home.

One day, Akira musters the courage to visit Nanako's house to deliver some school materials. There, he encounters Nanako's grandfather, Manzou Momoi, an eccentric and somewhat lazy mad scientist who has just completed a strange new invention. Before Akira can fully comprehend the situation, he is caught up in one of Manzou's experiments. An accident with the machine causes Akira and Nanako to swap bodies entirely, trapping the timid Akira inside Nanako's petite body and the aggressive Nanako inside Akira's male form.

Complicating matters, the machine is broken in the process, leaving the pair stuck in each other's lives. While Akira is desperate to return to his original body and maintain his masculinity, Nanako finds herself thrilled with the situation. Her naturally rough and assertive personality makes her perfectly suited to life as a boy, and she begins to enjoy her newfound freedom. At school, the situation creates a web of confusion. Akira, now in Nanako's body, inadvertently softens her image with his polite and gentle demeanor, making him incredibly popular with the boys, including his own best friend, Shinnosuke Senbongi, who becomes enamored with this new "Nanako." Meanwhile, Nanako, in Akira's body, begins dating her friend Makoto Shiina, who is unaware of the switch and finds the suddenly bold and charismatic Akira attractive.

The primary narrative arc follows the duo's attempt to reverse the swap. Nanako's grandfather agrees to rebuild the machine but gives them a difficult ultimatum: they must raise a large sum of money for the repairs. This leads to a series of comedic efforts as Akira and Nanako take on odd jobs, including working in a maid cafe and at a resort in Okinawa. As they struggle to earn the cash, their savings are constantly depleted, often to pay off Nanako's debts or due to other mishaps. Throughout this process, Akira begins to experience life from a female perspective, and Nanako learns about the social pressures Akira faces as a less assertive male. The narrative explores this strange romantic triangle and the quartet of relationships, focusing on the growing, unconventional bond between Akira and Nanako as they navigate their swapped lives. The story concludes on an open-ended note as the deadline passes and the grandfather leaves the country, forcing the pair to accept their new reality and continue saving money for his eventual return.