Handedness is one of the most obvious functional asymmetries, but its relation to an anatomical asymmetry of the hand representation area in the motor cortex has not been demonstrated. This would be a crucial test for the hypothesis of structure-function correlation in cortical motor organization. Using magnetic resonance morphometry, we show for the first time that the depth of the central sulcus is related to handedness. In right-handers, the left central sulcus is deeper than the right, and vice versa in left-handers. Macrostructural asymmetry is complemented by a microstructural left-larger-than-right asymmetry in neuropil volume (i.e., tissue compartment containing dendrites, axons, and synapses) in Brodmann's area 4. These asymmetries suggest that hand preference is associated with increased connectivity (demonstrated by an increased neuropil compartment in left area 4) and an increased intrasulcal surface of the precentral gyrus in the dominant hemisphere.