The purpose of the present study was to relate the expected inter-subject variability in voluntary drive of the knee extensor muscles during a sustained isometric contraction to the changes in firing rates of single motor units. Voluntary activation, as established with superimposed electrical stimulation was high (range: 91-99%, n=8) during a short maximal contraction, but was lower (range: 69-100%) in most subjects at the point of force failure during a sustained (49.1+/-10.1 s) fatiguing contraction at 50% of maximum force. On a different experimental day the firing behaviour of 27 single motor units was recorded with wire electrodes in the vastus lateralis muscle, 24 of which could be monitored from the time of recruitment to the point of force failure (53.6+/-9.8 s). Motor unit firing behaviour differed considerably among subjects. During the second half of the sustained, fatiguing contraction the changes in firing rate firing rate variability of early recruited units ranged from -10% to +100% and from -50% to +160% respectively among subjects. There were significant positive linear relations between voluntary activation, on the one hand, and rectified surface electromyogram (rsEMG, r=0.82), the changes in motor unit firing rate ( r=0.49) and firing rate variability ( r=0.50) towards the point of force failure on the other. The present data suggest that differences in voluntary drive that appear among subjects during fatigue may be an important determinant of motor unit firing behaviour.