Apart from exciting corticospinal cells and evoking a motor response, electrical or magnetic transcranial cortical stimulation (TCCS) delivered during voluntary activity produces a prolonged inhibition of activity, a silent period (SP), that can last up to 280 msec. The SP duration after TCCS is directly proportional to stimulus intensity. To determine the anatomic substrate and underlying physiological properties of the SP from TCCS, we (1) compared the SP from TCCS with the SP from cutaneous and mixed nerve stimulation, (2) studied the excitability cycle of spinal motor neurons in 3 double stimulus conditions: (a) after paired peripheral nerve stimulation, (b) after TCCS and peripheral nerve stimulation, and (c) after paired electrical TCCS, (3) investigated the timing of the excitability of the sensorimotor cortex measuring long latency responses from median nerve stimulation delivered inside the SP from TCCS. We found that after TCCS, spinal motor neuron segmental excitability is reduced for a period up to 100 msec. Inhibition at a suprasegmental, possibly cortical, level was even more prolonged for a period up to 160 msec, suggesting that at least the late part of the SP after TCCS is due to supraspinal inhibition. Determining the nature of the supraspinal inhibition such as the possible role of cortical inhibitory mechanisms may be useful in further understanding central mechanisms of voluntary motor control and sensorimotor processing.