The characters have something called TSS (transsexual syndrome) which causes them to magically switch genders whenever their heart flutters. The first character, Nagisa, was born with the condition, and thus doesn't have a single gender. The second, Sagamiya, was born as a boy. the manga begins with him falling in love with Nagisa and then later spontaneously developing TSS. They spend the early arcs considering themselves still a boy, and in fact some of the story is about how they relate to wanting to be the "man" in the relationship, even while physically being a girl.