Using the technique of transcranial magnetic stimulation over the motor areas of cortex and recording electromyographic (EMG) responses from the first dorsal interosseous muscle, we measured the excitability of corticocortical inhibitory circuits at rest using a double pulse paradigm, in 11 patients with Parkinson's disease (PD) studied both on (ON) and off (OFF) (after overnight withdrawal) their normal medication and in 10 age-matched control subjects. There was a significant decrease in the amount of corticocortical inhibition at short (1–5 msec) interstimulus intervals in patients relative to their controls, which improved after L-dopa intake. For comparison with previous reports using transcranial magnetic stimulation we also measured the duration of the EMG silent period when stimuli were given to voluntarily active muscle, and the threshold for evoking an EMG response in both the active and relaxed states. There was no change in the threshold for evoking EMG responses whether muscles were active or relaxed. However, the silent period was significantly prolonged when ON compared with OFF, although in neither state was the duration significantly different from that seen in normals. We suggest that there may be abnormalities of motor cortical inhibitory mechanisms in patients with Parkinson's disease that are not readily detected using threshold or silent period measurements alone.