In humans, the rostral part of the ventral premotor cortex (PMv), the homologue of F5 in monkeys, is known to be critically involved in shaping the hand to grasp objects. How does information about hand posture, that is processed in PMv, give rise to appropriate motor commands for transmission to spinal circuits controlling the hand? Whereas PMv is crucial for skilled visuomotor control of the hand, PMv sends relatively few direct corticospinal projections to spinal segments innervating hand muscles and the most likely route for PMv to contribute to the control of hand shape is through cortico-cortical connections with primary motor cortex (M1). If this is the case, we predicted that PMv-M1 interactions should be modulated specifically during precision grasping in humans. To address this issue, we investigated PMv-M1 connections by means of paired-pulse transcranial magnetic stimulation (TMS) and compared whether they were differentially modulated at rest, and during precision versus power grip. To do so, TMS was applied over M1 either in isolation or after a conditioning stimulus delivered, at different delays, over the ipsilateral PMv. For the parameters of TMS tested, we found that, at rest, PMv exerted a net inhibitory influence on M1 whereas, during power grip, this inhibition disappeared and was converted into a net facilitation during precision grip. The finding that, in humans, PMv-M1 interactions are selectively modulated during specific types of grasp provides further evidence that these connections play an important role in control of the hand.