1. (1) The mechanism underlying muscle fatigue has been studied in maintained isometric maximal contraction of the wrist flexor muscles under normal and ischaemic conditions. Automatic EMG analysis has been used to show the level of motor unit firing rates in fatiguing contractions. 2. (2) Under non-ischaemic conditions the decay of force, turns and amplitude is about the same, whereas during ischaemia force and to a lesser extent amplitude pulses, decline steeply towards zero, while turns, representing the number of impulses, remain in the non-ischaemic range. 3. (3) Depending on the duration of the ischaemia applied before contraction, force and amplitude are initially reduced but turns are nearly unchanged compared with the non-ischaemic values. It is suggested, that this is due to nerve blocking of high threshold motor units. 4. (4) The results show that transmission failure at the neuromuscular junction is a minor factor in muscle fatigue and that this structure is not greatly affected by ischaemia. 5. (5) It is believed that in the first phase of muscle fatigue the force decline is connected with a slowing of discharge rates. This change of firing frequencies with time must be considered optimal in respect to the force produced because higher as well as lower discharge rates would reduce the force development. In the later phase it is possible that contractile element fatigue, connected with a reduction of action potential amplitudes of single muscle fibres, predominates, especially when the blood supply is obstructed.