1. The mechanism of fatigue has been studied in maintained maximal voluntary contractions of the first dorsal interosseous muscle of the hand.2. Fatigue occurs in two phases. In the first, lasting 1 min, force falls to about 50%. The smoothed rectified e.m.g. (s.r.e.) falls with the same time course and the normal linear relation between s.r.e. and force of unfatigued muscle is preserved.3. In the second phase, force falls relatively faster than s.r.e.4. Arterial occlusion does not affect the first phase, but in the second phase causes force to fall to zero, whereas without occlusion it tends to stabilize at about 25%.5. The size of the synchronous muscle action potential evoked by ulnar nerve stimulation falls to about 65% of normal, most of this fall occurring in the first phase.6. During recovery after prolonged fatigue, the relation between force and s.r.e. is changed for weak voluntary contractions much more than for strong ones, such that force is less for a given s.r.e. than normal.7. These results are interpreted as evidence that, in a maximal voluntary contraction, neuromuscular junction fatigue is most important at first, but later, contractile element fatigue increases, particularly when the blood supply is obstructed.8. Neuromuscular junction fatigue is believed to be most marked in high threshold motor units, while contractile element fatigue more especially affects low threshold units.