Vagus nerve stimulation (VNS) is used as adjunctive treatment for medically refractory epilepsy, but little is known about its mechanisms of action. The effects of VNS on the excitatory and inhibitory circuits of the motor cortex were evaluated in five patients with epilepsy using single- and paired-pulse transcranial magnetic stimulation (TMS). Patients were examined with the stimulator on and off. VNS determined a selective and pronounced increase in the inhibition produced by paired-pulse TMS with no effects on the excitability by single-pulse TMS.