In this study, we have used paired transcranial stimulation of the motor cortex to test the hypothesis that cortical inhibition is decreased in juvenile myoclonic epilepsy (JME). The double shock technique was adopted here because it offers a means for highlighting abnormal inhibitory mechanisms. From previous experiments performed on healthy subjects, it is known that a magnetic conditioning stimulus, of subthreshold intensity, suppresses the MEP in response to a subsequent suprathreshold stimulus delivered after 1-4 msec. JME patients were selected as a potential contrast with other forms of idiopathic generalized epilepsy, because they complain of myoclonic jerks without loss of consciousness, indicating with certainty a dysfunction of the motor cortex. Two patients with sporadic grand mal and one non-epileptic patient were also investigated. Paired stimulation was produced by a Bi-stim (Magstim) stimulator, with a figure-of-8 coil placed over the hand area of the motor cortex, and a set of interstimulus intervals (ISIs) ranging from 1 to 6 msec was analyzed. In JME patients there were two indications of abnormality with respect to normal subjects and to the other epileptic patients: (1) the absence of MEP suppression to paired stimulation; (2) a progressive amplitude increase of MEPs to the test stimulus alone. In the two patients with the other form of epilepsy the pattern of inhibition was broadly preserved, even though there was some difference from the normal profile. The results suggest that the loss of MEP inhibition can be regarded as a marker of JME.