Changes of local synaptic activity during acquisition of a visuomotor skill were examined with positron emission tomography (PET) imaging of regional cerebral blood flow (rCBF). Eight subject learned the pursuit rotor task, a predictable tracking task, during three sequential PET scans (day 1). Subjects returned 2 days later and repeated the three pursuit trials and PET scans (day 2) after completing an extensive practice session. Control scans without movement bracketed the pursuit trials on both days to rule out time effects unrelated to motor skill learning. PET images were transformed to a common stereotaxic space using matched magnetic resonance imaging (MRI) scans. Group learning effects were determined by a repeated measures multivariate analysis of variance (ANOVA). During motor skill acquisition (day 1), increases of synaptic activity were identified in cortical motor areas and cerebellum, supporting the hypothesis that procedural motor learning occurs in motor execution areas. During long‐term practice (day 2), changes were limited to the bilateral putamen, bilateral parietal cortex, and left premotor cortex. To characterize differences in the rate of learning between subjects, each subject's performance data from day 1 was fit with a power function. The exponents were correlated with rCBF data on a pixel‐by‐pixel basis. Rapid skill acquisition was associated with increasing rCBF in premotor, prefrontal, and cingulate areas, and decreasing rCBF in visual processing areas located in the temporal and occipital cortex. This pattern in fast learners may reflect a more rapid shift from a visually guided strategy (accessing perceptual areas) to an internally generated model (accessing premotor and prefrontal areas). © 1994 Wiley‐Liss, Inc.