Most people are right-handed, preferring the right hand for skilled as well as unskilled activities, but a notable proportion are mixed-handed, preferring to use the right hand for some actions and the left hand for others. Assuming a structural/functional correlation in the motor system we tested whether asymmetries in hand performance in consistent right and left handers as well as in mixed handers are associated with anatomical asymmetries in the motor cortex. In vivo MR morphometry was used for analyzing interhemispheric asymmetry in the depth of the central sulcus in the region of cortical hand representation of 103 healthy subjects. Subjects were tested both for hand preference and hand performance. As expected, left-right differences in hand performance differed significantly between consistent right, consistent left and mixed handers and were independent on gender. Male consistent right handers showed a significant deeper central sulcus on the left hemisphere than on the right. Anatomical asymmetries decreased significantly from male consistent right over mixed to consistent left handers. Sixty two per cent of consistent left handers revealed a deeper central sulcus on the right than on the left hemisphere, but for the group as a whole this rightward asymmetry was not significant. No interhemispheric asymmetry was found in females. Thus, anatomical asymmetry was associated with handedness only in males, but not in females, suggesting sex differences in the cortical organization of hand movements.