To understand the neural factors which contribute to fatigue, it is not satisfactory to regard fatigue as occurring only when a task can no longer be performed. Changes in muscle afferent feedback, moto neuronal discharge, moto cortical output, and perceived effort develop well before an endurance limit in limb muscles. During sustained maximal contractions the discharge of moto neurones declines, commonly to below the level required to produce maximal force from the muscle whose contractile speed is usually slowed. Thus, some `central' fatigue develops. Recent findings using transcranial stimulation have revealed that the moto cortex is one site at which suboptimal output develops during human muscle fatigue. There is a need to study the reflex effects on moto neurones and the excitability of the moto cortex in experimental animals, as well as to apply rigorous methods to assess these processes in voluntary exercise in human subjects.