We tested the hypothesis that transcranial magnetic stimulation (TMS), in addition to its inhibitory action on the corticospinal output, can also exert some inhibitory effect on the transcallosal system connecting the two motor cortices. In seven normal subjects, instructed to keep their right opponens pollicis (OP) muscle fully relaxed and their left OP muscle voluntarily contracted, we used a paired-pulse TMS protocol, to stimulate the left motor cortex. We evaluated the effect of low-intensity conditioning stimulation on the ipsilateral silent period (iSP) elicited by the subsequent test stimulus. Compelling evidence exists to support that this iSP is mediated by the activation of transcallosal motor fibres. Simultaneously, the inhibition of the motor evoked potential (MEP) in the right OP muscle was also investigated. At the interstimulus interval (ISI) of 3 ms, the iSP was significantly (P<0.0001, repeated-measures ANOVA) suppressed by conditioning intensities ranging from 1.2 to 0.6 of MEP threshold. The assessment of the time-course showed that iSP inhibition was present in all the tested subjects only at ISIs of 2 and 3 ms (for each subject P<0.05, repeated-measures ANOVA). Several findings suggest that the suppression of iSP is brought about by the activation of inhibitory mechanisms operating in the stimulated (left) motor cortex. We propose that the assessment of iSP suppression could be a method to study the excitability of intracortical inhibitory circuits in the affected hemisphere of patients with unilateral damage of the corticospinal tract.