Transcranial magnetic stimulation (TMS) causes the corticospinal system to become refractory to subsequent stimuli for up to 200 ms. We examined the phenomenon of paired pulse inhibition with TMS under conditions of rest, ongoing voluntary activation (isometric force generation), and at variable delays following activation (postactivation) of the wrist extensors of seven normal subjects. Paired stimuli were delivered to the motor cortex with a circular coil at 1.1 times motor evoked potential (MEP) threshold, with various interstimulus intervals. Voluntary activation caused a marked decrease in the variability of the ratio of the amplitude of the MEP evoked by the test pulse to that of the MEP evoked by the conditioning pulse. Marked inhibition of the MEP evoked by the test pulse was still present. Postactivation, however, caused a dramatic reversal of the inhibitory effect of the conditioning pulse in all subjects at interstimulus intervals ranging from 40 to 120 ms. This effect lasted for up to 10 s following the cessation of activation. MEPs to transcranial electrical stimulation were also inhibited by conditioning TMS, but postactivation did not reverse this inhibition, indicating that the reversal of paired pulse inhibition is intracortical. We conjecture that paired pulse inhibition reflects activity of inhibitory interneurons or inhibitory connections between cortical output cells that are inactivated in the postactivation state.