With fatigue, force generation may be limited by several factors, including impaired impulse transmission and/or reduced motor drive. In 5-min isometric maximal voluntary contraction, no decline was seen in the peak amplitude of the tibialis anterior compound muscle mass action potential (M wave) either during or immediately after the voluntary effort, provided maximal nerve stimulation was retained. For first dorsal interosseous (FDI) muscle, M wave amplitudes declined by 19.4 +/- 1.6% during the first 2 min but did not change significantly thereafter, despite the continued force reduction (up to 94% in 5 min for both muscles). The duration of the FDI M waves increased (greater than 30%), suggesting that the small decline in amplitude was the result of increased dispersion between the responses of different motor units. Some subjects kept FDI maximally activated throughout, but when they used tibialis anterior, twitch occlusion and tetanic muscle stimulation showed that most subjects were usually only able to do so for the first 60 s and thereafter only during brief "extra efforts." Thus force loss during isometric voluntary contractions sustained at the highest intensities results mainly from failure of processes within the muscle fibers.