Sex differences in mental rotation tasks, favoring men, have been noted in behavioral studies and functional imaging studies. In the present study ten female and ten male volunteers underwent functional magnetic resonance imaging in a conventional block design. Regions of activation were detected after performance of a mental rotation task inside the scanner. In contrast to previous studies, confounding factors such as performance differences between genders or high error rates were excluded. Men showed significantly stronger parietal activation, while women showed significantly greater right frontal activation. Our results point to gender specific differences in the neuropsychological processes involved in mental rotation tasks.