In this study, we investigated blood-flow-related magnetic-resonance (MR) signal changes and the time course underlying short-term motor learning of the dominant right hand in ten piano players (PPs) and 23 non-musicians (NMs), using a complex finger-tapping task. The activation patterns were analyzed for selected regions of interest (ROIs) within the two examined groups and were related to the subjects' performance. A functional learning profile, based on the regional blood-oxygenation-level-dependent (BOLD) signal changes, was assessed in both groups. All subjects achieved significant increases in tapping frequency during the training session of 35 min in the scanner. PPs, however, performed significantly better than NMs and showed increasing activation in the contralateral primary motor cortex throughout motor learning in the scanner. At the same time, involvement of secondary motor areas, such as bilateral supplementary motor area, premotor, and cerebellar areas, diminished relative to the NMs throughout the training session. Extended activation of primary and secondary motor areas in the initial training stage (7-14 min) and rapid attenuation were the main functional patterns underlying short-term learning in the NM group; attenuation was particularly marked in the primary motor cortices as compared with the PPs. When tapping of the rehearsed sequence was performed with the left hand, transfer effects of motor learning were evident in both groups. Involvement of all relevant motor components was smaller than after initial training with the right hand. Ipsilateral premotor and primary motor contributions, however, showed slight increases of activation, indicating that dominant cortices influence complex sequence learning of the non-dominant hand. In summary, the involvement of primary and secondary motor cortices in motor learning is dependent on experience. Interhemispheric transfer effects are present.