Age-related structural brain changes have been demonstrated repeatedly but data on the effect of gender on age-related structural brain changes are conflicting. Using high-resolution T1-weighted magnetic resonance imaging and voxel-based morphometry, we examined a population of 133 healthy adults (women, 73; men, 60; age range, 29-80 years) focusing on differential aging between men and women (i.e., interaction of age and gender). Compared to women, men showed accelerated age-related gray matter (GM) loss in the posterior putamen. Our data may constitute the structural substrate for age-related differences in motor function between men and women such as the higher incidence and earlier onset of Parkinson's disease in men.