The testosterone derivative 4,16-androstadien-3-one (AND) and the estrogen-derived steroid estra-1,3,5(10),16-tetraen-3-ol (EST) are compounds believed to be human pheromones. AND is predominantly found in male sweat, while EST is most abundant in the urine of females. In a previous positron emission tomography study, we discovered that the inhalation of AND and EST activated regions responsible for sexual dimorphism in the anterior hypothalamus, and this activation varied depending on gender and relationship status. In the current study, the activation pattern induced by AND and EST was compared among homosexual males, heterosexual males, and heterosexual females. Unlike heterosexual males, homosexual males showed hypothalamic activation in response to AND stimulation, similar to heterosexual females. The maximum level of activation was observed in the medial preoptic area, in the anterior part of the hypothalamus, which, based on animal studies, is closely associated with sexual behaviors (the region is considered a central center for erection – translator’s note). In contrast to presumed pheromones, traditional odors were processed similarly in all three groups examined and exclusively engaged the olfactory brain (amygdala, piriform cortex, and orbitofrontal cortex). The obtained data demonstrate that our brain responds differently to the two suspected pheromones compared to traditional odors and reveal a relationship between sexual orientation and hypothalamic neuronal processes.