A male advantage is often reported for measures of visuospatial performance, including measures of spatial navigation; however, few papers have addressed sex differences in brain activity during performance of these navigation tasks. We used functional MRI to compare the brain activation between young adult men and women during performance in a virtual environment (VE). Men and women did not differ in performance, but sex differences were apparent in the functional neuroanatomical correlates of navigation. In particular there was increased activation of the posterior cingulate retrosplenial cortex in men, and, in women with perfect recall performance, increased activation of the parahippocampal gyrus. These two areas are keys to successful navigation. Our results demonstrate that even when men and woman are well-matched on navigation performance, they appear to use different brain mechanisms to achieve the same behavioral end point.