Interhemispheric inhibition (IHI) between motor cortical areas is thought to play a critical role in motor control and could influence manual dexterity. The purpose of this study was to investigate IHI preceding movements of the dominant and nondominant hands of healthy volunteers. Movement-related IHI was studied by means of a double-pulse transcranial magnetic stimulation protocol in right-handed individuals in a simple reaction time paradigm. IHI targeting the motor cortex contralateral (IHI(c)) and ipsilateral (IHI(i)) to each moving finger was determined. IHI(c) was comparable after the go signal, a long time preceding movement onset, in both hands. Closer to movement onset, IHI(c) reversed into facilitation for the right dominant hand but remained inhibitory for left nondominant hand movements. IHI(i) displayed a nearly constant inhibition with a trough early in the premovement period in both hands. In conclusion, our results unveil a more important modulation of interhemispheric interactions during generation of dominant than nondominant hand movements. This modulation essentially consisted of a shift from a balanced IHI at rest to an IHI predominantly directed toward the ipsilateral primary motor cortex at movement onset. Such a mechanism might release muscles from inhibition in the contralateral primary motor cortex while preventing the occurrence of the mirror activity in ipsilateral primary motor cortex and could therefore contribute to intermanual differences in dexterity.