While the cortical effects of repetitive motor activity are generally believed to be task specific, the task parameters that modulate these effects are incompletely understood. Since there are differences in the neural control of flexor vs. extensor muscles, the type of muscles involved in the motor task of interest may be one important parameter. In addition, the role each muscle plays in the task, such as whether or not it is the prime mover, is another potentially important task parameter. In the present study, use-dependent cortical plasticity was examined in healthy volunteers performing a robotic waveform tracking task with either the extensor digitorum communis (EDC) or flexor digitorum superficialis (FDS) acting as the prime mover. Transcranial magnetic stimulation was used to measure corticospinal excitability (CE) and short-interval intracortical inhibition of lower and higher threshold corticospinal neurons (SICI(L) and SICI(H), respectively) before and after a flexion- or extension-resisted finger tracking task. After repetitive performance of the tracking task, there was a significant decrease in SICI(L) targeting the EDC, while no change in CE targeting EDC was observed. In contrast, the reverse pattern was observed in the FDS: a significant increase in CE with no change in SICI(L). There was also a tendency toward increased SICI(H) targeting whichever muscle was acting as the prime mover, although this effect did not reach statistical significance. We conclude that there is a difference in patterns of use-dependent plasticity between extrinsic finger flexor and extensor muscles performing the same task.