Single-pulse transcranial magnetic stimulation (s-TMS) with recording of motor evoked potentials (MEPs) from thenar muscles of both hands was performed on 84 patients with cryptogenic partial epilepsy and 50 healthy controls. We analyzed the cortical latency (CL), central conduction time (CCT), and threshold intensity (TI) required to elicit liminal MEPs at rest. In the patients, CL and CCT were normal, but TI was significantly higher than in the controls. Of the 84 patients, 65 were taking one or more antiepileptic drugs and 19 were untreated. The untreated patients had a significantly lower TI than the treated patients. In the treated patients, the TI increase paralleled the number of drugs taken. Additionally, in 2 subgroups of patients undergoing major modifications of antiepileptic treatment, TI dropped after partial withdrawal of medication and increased following the commencement of therapy. The results suggest that anticonvulsants depress the excitability of human motor pathways in epileptic subjects.