We used functional Magnetic Resonance Imaging (fMRI) to examine the distribution of cerebral activation related to prolonged skill practice. In a bimanual variant of the Serial Reaction Time Task (SRT), simultaneous finger movements of the two hands were made in response to randomly ordered pairs of visual stimuli (Double SRT, DoSRT). Extended practice by a week of daily performance resulted in gradual decrease of reaction times, associated with an increased involvement of the ventral putamen and globus pallidus, reaching statistical significance only on the left, side (Statistical Parametric Mapping, SPM99). This increase was complementary to a decrease of cortical activations. The striatal activation after training on random order stimuli indicates that the striatum is not exclusively involved in sequence learning. This extended function implies a role in the acquisition of basic visuomotor skills that includes the specific selection of the appropriate muscles in response to independent stimuli. (C) 2004 Elsevier B.V. All rights reserved.