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Background: Sex differences in eating behavior are well documented, but it is not known whether these differences have neuroanatomical correlates. Recent neuroimaging studies have provided functional maps of the human cerebral areas activated in response to hunger and satiation. Objective: The objective of this study was to assess whether the brain's response to a meal is sex-specific. Design: Using positron emission tomography, we measured regional cerebral blood flow, a marker of neuronal activity, to investigate the functional neuroanatomy of hunger (36-h fast) and satiation (in response to a liquid meal) in 22 women and 22 men. Results: We observed extensive similarities, as well as some differences, between the sexes. In response to hunger, the men tended to have greater activation in the frontotemporal and paralimbic areas than did the women (P < 0.005). In response to satiation, the women tended to have greater activation in the occipital and parietal sensory association areas and in the dorsolateral prefrontal cortex than did the men (P < 0.005); in contrast, the men tended to have greater activation in the ventromedial prefrontal cortex than did the women (P < 0.005). Conclusions: Despite extensive similarities in the brain responses to hunger and satiation between the men and women, our study showed sex-specific brain responses to a meal that indicate possible differences between men and women in the cognitive and emotional processing of hunger and satiation. This study provides a foundation for investigating the brain regions and cognitive processes that distinguish normal and abnormal eating behavior in men and women. Am J Clin Nutr 2002;75:1017-22. KEY WORDS Sex, hunger, satiation, eating behavior, positron emission tomography, human brain