Central fatigue is a subjective phenomenon which can be examined using transcranial magnetic stimulation (TMS). To assess central fatigue, we compared TMS and peripheral electrical stimulations in patients with central nervous system (CNS) lesions and controls before and after an exhaustive task. The recovery times of motor evoked potential (MEP) amplitudes were significantly prolonged in the patient group whereas the recovery of F waves and compound muscle action potentials showed no significant changes. The results indicate that fatigue cannot be attributed either to intramuscular processes or to reduced spinal excitability, but reflects a supraspinal, probably cortical phenomenon. The measurement of MEP recovery times proved to be a simple and objective tool for the assessment of fatigue and for the differentiation between healthy controls and patients with CNS lesions.