To examine changes in interhemispheric inhibition (IHI) during homologous muscle activation in healthy subjects and in people with hemiparesis.IHI in the abductor pollicus brevis (APB) muscle was examined using paired transcranial magnetic stimulation. Stimuli were delivered while the target APB was at rest or activated, and while the non-target contralateral APB was at rest or activated.In control subjects, IHI in the resting target APB was enhanced during activation of the contralateral APB, and was greater from the dominant hemisphere to the non-dominant. In stroke subjects, IHI in the non-affected APB was not modulated during voluntary activation of the affected APB, but was influenced by the prior dominance of affected hemisphere. Bilateral muscle activation did not elicit any changes in IHI in either group.IHI is asymmetrical between hemispheres but only when the target muscle is at rest. Subjects with stroke have an impaired ability to modulate IHI during unilateral muscle activation.In people with stroke, the extent and modulation of interhemispheric transfer is influenced by the prior dominance of the affected hemisphere. This may impact on the efficacy of treatment interventions incorporating bilateral activation.