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Men and women differ in cerebral organization and prevalence rates of eating disorders. However, no studies have yet examined sex differences in cerebral responses to the caloric content of food images. Sixteen healthy adults (eight men; eight women) underwent functional magnetic resonance imaging while viewing images of high-calorie and low-calorie foods. Compared with men, women showed significantly greater activation to calorie-rich foods within dorsolateral, ventrolateral, and ventromedial prefrontal cortex, middle/posterior cingulate, and insula. Men failed to show greater activation in any cortical region compared with women, although amygdala responses were greater in men at a more liberal threshold. When viewing high-calorie food images, women seem more responsive than men within cortical regions involved in behavioral control and self-referential cognition.