Magnetic motor-evoked potentials were recorded in 53 patients with medically intractable, mainly temporal lobe epilepsy and compared with potentials of 110 healthy volunteers. The motor-evoked potentials were reevaluated in 16 of the 53 patients after substantial reduction of antiepileptic drug doses. The objective was to assess the effect of epilepsy and of anticonvulsant medication on the central motor system. In subjects receiving antiepileptic treatment, cortical threshold intensities were markedly elevated and peripheral latencies were prolonged. Cortical threshold intensities and peripheral latencies decreased to approach control values after anticonvulsant medication was reduced but were increased in patients treated with 2 or 3 anticonvulsant agents instead of 1. Additionally, high levels of interictal epileptiform activity and a high frequency of seizures significantly decreased the central motor conduction time and, in part, threshold intensities. The central motor conduction time was further diminished after reduction of anticonvulsant treatment and increased when several drugs were administered. The duration of epilepsy, the location of the epileptic focus, and the type of the epileptic seizure did not affect motor-evoked potentials. Conclusively, central motor pathways are endogenously facilitated by epileptiform activity even if clinical signs of their involvement are absent. Anticonvulsant medication exerts major reversible effects on magnetic motor-evoked potentials.