During sustained voluntary contractions, the variability in motor unit interspike intervals increases with fatigue. This increase in variability may represent an adaptive mechanism to prevent fatigue. We investigated whether randomly modulating interpulse intervals (IPI) in a constant frequency stimulation protocol reduces force loss over time compared to a non-modulated constant frequency protocol. A second purpose of this study was to investigate the role of the M-wave in force generation during evoked contractions. Eight healthy subjects participated in three 3-minute fatigue protocols of the thenar muscles elicited by supramaximal stimulation of the median nerve. All three protocols had a mean IPI of 33.3ms and only differed in the type of modulation. One protocol consisted of 0% modulation ('Constant'), another protocol consisted of uniformly distributed modulation of [plus or minus]20% ('Variable'), and a third protocol consisted of ramped modulation from 0 to [plus or minus]20% ('Ramp'). There was no significant difference between overall force-time integrals for the three protocols. There was a significant reduction in M-wave amplitude for all three protocols; however, the M-wave immediately following the 'Ramp' protocol was significantly larger than the M-wave immediately following the 'Constant' protocol. We conclude that modulation is ineffective at preserving force output and somewhat effective at preserving the M-wave amplitude. The varied reductions in fatigued M-waves suggest that it is not necessarily a limiting factor in force output and that it was not necessarily linked to the force loss in this experiment. / text