The effect of muscle length on susceptibility to fatigue has been examined in human ankle dorsiflexor muscles. The fatiguing procedure consisted of either indirect tetanic stimulation at 20 Hz or maximal voluntary contraction; each procedure lasted 90 s. The amplitude of the evoked muscle compound action potential (M-wave) increased during the first 30 s or so of the tetanic fatiguing procedure and then decreased. The torque developed by the dorsiflexor muscles declined throughout the period of tetanization. A significantly greater reduction in twitch and tetanic torque was found after the fatiguing procedure had been conducted at the optimum muscle length rather than with the muscle in a shortened position. Relaxation after tetanic stimulation was slower after fatigue had been induced at the optimum muscle length. It is concluded that muscle fatigue is related to the number of actin-myosin cross-bridge interactions and is unlikely to be accounted for solely on the basis of changes in the ionic composition of the transverse tubular fluid.