Transcranial magnetic stimulation was used to study motor evoked potentials (MEPs) of leg muscles in controls and patients with multiple sclerosis (MS) before and after walking. In controls, MEP areas were significantly reduced after walking. A similar or greater reduction was seen in most patients, although there was a wide range of values. The M waves were unchanged. We conclude that walking induces functional changes of the corticospinal system and/or connected neurons contributing to central fatigue, especially in patients with MS.