In common with other secondary motor areas, the macaque ventral premotor cortex (PMv) gives rise to corticospinal projections; it also makes numerous reciprocal corticocortical connections with the primary motor cortex (M1). Repetitive intracortical microstimulation (rICMS) of the PMv gives rise to movements of the hand and digits. To investigate whether these motor effects are dependent on the corticocortical interactions with M1, the effect of reversible inactivation of the M1 hand area was tested in three macaque monkeys with chronically implanted intracortical electrodes in the hand representations of M1 and PMv (rostral division, area F5). Monkeys were lightly sedated. Test EMG responses to rICMS were recorded from intrinsic hand muscles before and after microinjection of the GABA agonist muscimol in the M1 hand area. This not only greatly reduced EMG responses evoked from M1, but also reduced or abolished responses from F5, over a similar time course (20-50 min). Muscimol in M1 reduced the level of background EMG activity in the contralateral hand, which was paretic for several hours after injection. However, because EMG responses to direct activation of the corticospinal tract were significantly less affected than the responses to F5 stimulation, it is unlikely that reduced motoneuronal excitability explained the loss of the evoked responses from F5. Finally, muscimol injections in M1 greatly reduced the corticospinal volleys evoked by rICMS in F5. The results suggest that the motor effects evoked from F5 depend, at least in part, on corticocortical interactions with M1, leading to activation of M1 corticospinal outputs to hand muscles.