The control of motor units and the regulation of muscle force during sustained isometric contractions are still subject to debate. We have developed a model to simulate the behavior of motoneurons and the generation of muscle force in the first dorsal interosseous (FDI) and vastus lateralis (VL) muscles. The model sheds light on the mechanisms of muscle force regulation during isometric tracking tasks sustained to the endurance limit, on the changes in motor unit firing behavior and on the cause of increased force fluctuation with fatigue. The input to the model consists of an excitatory signal representing the sum of all excitatory and inhibitory inputs to the muscle. The input excitation is common to all the motor units in the pool of the muscle following the “common drive” concept, which states that all motor units are modulated by a common source [1]. The model describes a non-linear relation between the input excitation to the motoneuron pool and the firing rates of motor units [2], to which synaptic noise is added [3]. Motor unit firing rates follow the “onion skin” principle [4], which describes a hierarchical relationship between recruitment threshold and firing rates, with later-recruited motor units having progressively lower firing rates than earlier-recruited motor units. The model generates the motor unit mechanical responses (force twitches) [5], whose amplitude is altered with contraction time to replicate the initial increase (as a result of muscle potentiation) and subsequent decrease (as a result of muscle fatigue) in force generating capacity reported during sustained muscle activation [6-7]. The force contributions of the active motor units are computed by convolving each motor unit firing train with their respective force twitch, and are summed to obtain the simulated muscle force. A feedback loop adjusts the value of the input excitation so that the simulated muscle force is maintained at a value similar to that of a target force, mimicking the performance of force-tracking tasks. We modeled the force produced by the FDI and VL muscles during a series of repeated force contractions sustained at 50% and 20% MVC until the endurance limit, i.e., until the force could no longer be maintained at the target level. The model behavior was validated by comparing the simulated motor unit firing rate and force output with experimental evidences derived from a similar protocol of repeated contractions [6-7]. For both muscles, the model predicts the initial decrease and subsequent increase in motor unit firing rates which occur during sustained muscle activation as motor unit force twitches vary. A greater number of motor units are progressively activated as the simulation approaches the endurance limit. Increasing force fluctuations are observed as fatigue develops, likely due to the recruitment of higher-threshold higher-twitch amplitude motor units. Throughout the contraction series, the force produced by the VL muscle is smoother than that produced by the FDI muscle, probably due to the different mechanical characteristics of the two muscles. The results of the simulations reproduce the motor unit firing rate behavior and the increase in force fluctuations observed in previous empirical data during a similar protocol of repeated contractions [6-7]. Motor unit twitch force is the only parameter allowed to change with contraction time in the model. These results strongly suggest that, during voluntary isometric contractions, the excitation to the motoneuron pool is adjusted to compensate for the varying muscle-force generating capacity.