SUMMARY1. The main purpose of this study was to examine the effects of two subtly different stimulus patterns on the force developed by fast-twitch, fatiguable motor units in a cat hindlimb muscle during control (pre-fatigue) and fatiguing contractions.2. The peak force and the force-time integral responses of nineteen high fatigue (FF) and three intermediate fatigue (FI) motor units of the tibialis posterior muscle in five deeply anaesthetized adult cats were measured at selected times during the course of a 360-s fatigue test.3. The fatigue test involved a pseudo-random alternation of two patterns of stimulation. One pattern (regular) was composed of a train of stimuli with constant interpulse intervals, set at 1-8 x the twitch contraction time of each unit (interval range, 27-51 ms), and delivered for 500 (or 400) ms. For the total (FF + FI) motorunit sample, the mean (±S.D.) stimulation frequency was 26 + 4 Hz (range, 19-37 Hz). The other stimulus pattern (optimized) consisted of three initial stimuli with short (10 ms) interpulse intervals, followed by a constant interpulse-interval train that was adjusted (interval range, 29-62 ms; frequency, 23 + 5 Hz; frequency range, 16-36 Hz) such that the total train had the same number of pulses, and the same average frequency and duration as the regular train.4. The stimulus trains were delivered at 1 s-5 for 360 s, using three-train sequences of each pattern, randomly alternating with one another. The response of the third train in each sequence was selected for the force measurements. The force profile obtained from the fatigue test was subsequently decomposed into two profiles: one attributable to regular and one to optimized stimulation.5. During the initial responses to the fatigue test, the optimized stimulus pattern produced significantly more force than the regular stimulus pattern. For FF units, the mean increase in peak force (141 %) was significantly greater than the increase in the force-time integral (59 %).6. All motor units exhibited an initial potentiation of peak force with the regular stimulation pattern, whereas peak force declined monotonically with the optimized pattern. In contrast, the force-time integral potentiated in the first 30 s for both regular and optimized stimulus patterns. L. BEVAN AND OTHERS 7. Each motor unit maintained an increased force response to optimized stimulation during the fatigue test, with the greatest relative increase occurring about 120 s into the test, well after the potentiation effect had subsided. At 360 s of stimulation, the force enhancement with optimization was still substantial (83 % for peak force and 37 % for the force-time integral), yet force was virtually non-existent in response to regular stimulation.8. These results suggest that subtle changes in the activation pattern are a potential mechanism by which the central nervous system might increase force during fatigue. Furthermore, force optimization and potentiation seem to be motorunit properties that are as fundamental as the more conventionally stu...