We studied the effects of a loading dose of phenytoin on motor cortex excitability in five healthy volunteers. Phenytoin elevated motor thresholds to transcranial magnetic stimulation (TMS) in all subjects, but had no effects on motor-evoked potential amplitudes, silent period durations, and intracortical excitability tested by paired TMS during rest and voluntary muscle activation. These results are consistent with the hypothesis that blockade of voltage-gated sodium channels decreases membrane excitability and elevates the threshold to TMS, but will not reduce intracortical excitability.