The interhemispheric interactions between homologous wrist extensor and flexor muscles representations in the right and left primary cortex (M1) were studied using a paired-pulse transcranial magnetic stimulation in healthy subjects. The magnitude of interhemispheric inhibition (IHI) was studied in 9 right-handed subjects at short (10 ms, SIHI) and long (40 ms, LIHI) interstimulus intervals between the magnetic conditioning (CS) and test stimulus in the motor dominant to non-dominant cortex and vice versa, while the right or left hand was at rest or performing a unimanual sustained tonic contraction (holding a pen with the hand contralateral to the CS). A bidirectional powerful interhemispheric inhibition could be elicited at the short and long IHI phases (SIHI and LIHI) in wrist extensor and flexor muscles in most of the subjects at rest. SIHI but not LIHI was significantly bidirectionally reduced during unimanual contraction of the hand contralateral to the CS stimulation in comparison with rest. The amount of IHI after the stimulation of the "non-dominant" right hemisphere was not reduced in comparison with IHI after stimulation of the "dominant" left hemisphere whatever the active or resting condition. IHI directed to the wrist muscles had a similar level than IHI directed to digit muscles (FDI) at rest. Our data indicate that contralateral wrist muscles activity evokes a global, bidirectional reduction in IHI which was more pronounced for SIHI. These results provide additional evidence that changes in interhemispheric interactions between the M1s are involved in the control of unimanual movements including suppression of unwanted motor activity in the opposite limb during unilateral movements.