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There is evidence that the cerebellum is involved in motor learning and cognitive function in humans. Animal experiments have found structural changes in the cerebellum in response to long-term motor skill activity. We investigated whether professional keyboard players, who learn specialized motor skills early in life and practice them intensely throughout life, have larger cerebellar volumes than matched non-musicians by analyzing high-resolution T1-weighted MR images from a large prospectively acquired database (n=120). Significantly greater absolute (P=0.018) and relative (P=0.006) cerebellar volume but not total brain volume was found in male musicians compared to male non-musicians. Lifelong intensity of practice correlated with relative cerebellar volume in the male musician group (r=0.595, P=0.001). In the female group, there was no significant difference noted in volume measurements between musicians and non-musicians. The significant main effect for gender on relative cerebellar volume (F=10.41, P < 0.01), with females having a larger relative cerebellar volume, may mask the effect of musicianship in the female group. We propose that the significantly greater cerebellar volume in male musicians and the positive correlation between relative cerebellar volume and lifelong intensity of practice represents structural adaptation to long-term motor and cognitive functional demands in the human cerebellum.