A number of studies have shown a relationship between "sexual orientation" and size of various brain nuclei. We hypothesized that neurotransmitter differences might parallel neuroanatomical differences in the hypothalamus. We administered 40 mg of fluoxetine as a challenge to the serotonergic systems of exclusively homosexual and exclusively heterosexual men and measured cerebral metabolic changes with fluorodeoxyglucose positron emission tomography (FDG-PET). The metabolic differences we observed might reflect underlying neurochemical differences between homosexual and heterosexual men.