We studied the effects of exercise on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in 18 normal (control) subjects and 11 medication-free patients with cerebellar degeneration. Subjects performed repeated sets of isometric exercise of the extensor carpi radialis muscle until the muscle fatigued (subject became unable to maintain half maximal force). MEPs were recorded before and after each exercise set and for up to 30 minutes after the last set. The mean amplitude of MEPs recorded from the resting muscle immediately after each exercise set was 218% of the mean preexercise MEP amplitude in normal subjects and 132% in cerebellar patients, indicating postexercise MEP facilitation in both groups. However, postexercise MEP facilitation, compared with the mean preexercise MEP amplitude, was not significant in the patients but was significant in the normal subjects. The amplitudes of MEPs recorded within the first few minutes after fatigue were 44% of the mean preexercise MEP amplitudes in both groups. We conclude that in patients with cerebellar degeneration, postexercise MEP facilitation is significantly reduced, whereas postexercise MEP depression after fatigue is similar to that of normal subjects.