Fatigue of voluntary muscular effort is a complex and multifaceted phenomenon. Fatigue of peripheral nervous system components, including the contractile apparatus and the neuromuscular junction, has been well studied. Central nervous system components also fatigue, but studies have lagged for want of objective methods. Transcranial magnetic stimulation is a relatively new technique that can be used to assess central nervous system excitability from the motor cortex to the alpha-motoneuron. In six normal volunteers, including four of the investigators, the amplitudes of motor evoked potentials elicited by transcranial magnetic stimulation were transiently decreased after exercise, indicating fatigue of motor pathways in the central nervous system. The decrease in amplitude was associated with a feeling of fatigue. The mechanism of this phenomenon is apparently decreased efficiency in the generation of the motor command in the motor cortex.