Noninvasive transcranial magnetic stimulation (TMS) of the motor cortex not only induces short-latency, motor-evoked potentials (MEP) in contralateral muscles, but also inhibitory phenomena. One type of inhibitory action appears directly after the MEP in contralateral muscles and can be visualized by blockade of tonic, voluntary electromyographic (EMG) activity (postexcitatory inhibition, PI). Evidence for a cortical origin of PI, especially in its later part, was derived from double cortical stimulation in previous studies and is further supported by examination of PI in patients with focal hemispheric unilateral brain lesions in the present study. Thirty patients with different sites of vascular or tumour lesions were studied by TMS. In 6 patients with circumscribed lesions of the primary sensorimotor cortex a significant shortening of PI to contralateral muscles was observed. In 7 patients with focal lesions of the thalamus or internal capsule, in 6 patients with lesions of the premotor cortex and in 5 patients with lesions restricted to the parietal or temporal lobe, a significant prolongation of PI to the contralateral muscles was detected. Six patients with transient ischemic attacks showed either prolongation or shortening of PI. We conclude that PI is predominantly generated in the primary motor cortex, correspondingly its damage causes shortening of PI. In contrast, damage to brain areas that project to the primary motor cortex is followed by prolongation of PI. This remote effect on the primary motor cortex may result from disinhibition of cortical interneurones.