Movement representations within the human primary motor and somatosensory cortices can be altered by motor learning. Decreases in local GABA concentration and its release may facilitate this plasticity. Here we use in vivo magnetic resonance spectroscopy (MRS) to noninvasively measure serial changes in GABA concentration in humans in a brain region including the primary sensorimotor cortex contralateral to the hand used for an isometric motor sequence learning task. Thirty minutes of motor sequence learning reduced the mean GABA concentration within a 2 x 2 x 2-cm3 voxel by almost 20%. This reduction was specific to motor learning: 30 min of similar, movements with an unlearnable, nonrepetitive sequence were not associated with changes in GABA concentration. No significant changes in GABA concentration were found in the primary sensorimotor cortex ipsilateral to the hand used for learning. These changes suggest remarkably rapid, regionally specific short-term presynaptic modulation of GABAergic input that should facilitate motor learning. Although apparently confined to the contralateral hemisphere, the magnitude of changes seen within a large spectroscopic voxel suggests that these changes occur over a wide local neocortical field.