Men are generally more interested in and responsive to visual sexually arousing stimuli than are women. Here we used functional magnetic resonance imaging (fMRI) to show that the amygdala and hypothalamus are more strongly activated in men than in women when viewing identical sexual stimuli. This was true even when women reported greater arousal. Sex differences were specific to the sexual nature of the stimuli, were restricted primarily to limbic regions, and were larger in the left amygdala than the right amygdala. Men and women showed similar activation patterns across multiple brain regions, including ventral striatal regions involved in reward. Our findings indicate that the amygdala mediates sex differences in responsiveness to appetitive and biologically salient stimuli; the human amygdala may also mediate the reportedly greater role of visual stimuli in male sexual behavior, paralleling prior animal findings.