We studied the effect of varying interstimulus intervals (ISI) on the motor evoked potentials (MEP) using paired transcranial magnetic stimulation (PTMS) during relaxation and voluntary contraction of the abductor pollicis brevis. At ISI > or = 10 ms two independent MEPs could be evoked. At ISIs between 12-30 ms the amplitudes of the MEPs evoked by the second (test) stimuli had larger amplitude and shorter latencies than the MEPs evoked by the first (conditioning) stimuli. At an ISI of 50 ms the second MEP were similar to the first, between 75 and 100 ms the second MEPs were inhibited and at ISI of 200 and 400 ms the second MEPs showed almost similar amplitudes and latencies compared to the first. During voluntary contraction, the amplitudes of the first MEPs was higher compared to relaxed responses. The amplitudes of the second MEPs showed a similar pattern as the relaxed responses, but with a relatively smaller increase between 12-30 ms (p < 0.01), and less inhibition at 75 and 100 ms (p < 0.01). The study shows that conditioning stimuli 12-30 ms before the test stimulus facilitates the second MEP, and an ISI between 75-100 ms inhibit the second MEP. Voluntary contraction exerts a facilatory effect and reduce inhibition in the corticospinal neurons. These findings may reflects the changes in excitability and inhibition in the cortico-spinal neurons.