This study examined the effects of extended sessions of heavy intermittent exercise on quadriceps muscle fatigue and weakness. Twelve untrained volunteers (10 men and 2 women), with a peak oxygen consumption of 44.3 ± 2.3 ml·kg−1·min−1, exercised at ∼91% peak oxygen consumption for 6 min once per hour for 16 h. Muscle isometric properties assessed before and after selected repetitions (R1, R2, R4, R7, R12, and R15) were used to quantitate fatigue (before vs. after repetitions) and weakness (before vs. before repetitions). Muscle fatigue at R1 was indicated by reductions ( P < 0.05) in peak twitch force (135 ± 13 vs. 106 ± 11 N) and by a reduction ( P < 0.05) in the force-frequency response, which ranged between ∼53% at 10 Hz (113 ± 12 vs. 52.6 ± 7.4 N) and ∼17% at 50 Hz (324 ± 27 vs. 270 ± 30 N). No recovery of force, regardless of stimulation frequency, was observed during the 54 min between R1 and R2. At R2 and for all subsequent repetitions, no reduction in force, regardless of stimulation frequency, was generally found after the exercise. The only exception was for R2, where, at 20 Hz, force was reduced ( P < 0.05) by 18%. At R15, force before repetitions for high frequencies (i.e., 100 Hz) returned to R1 (333 ± 29 vs. 324 ± 27 N), whereas force at low frequency (i.e., 10 Hz) was only partially ( P < 0.05) recovered (113 ± 12 vs. 70 ± 6.6 N). It is concluded that multiple sessions of heavy exercise can reverse the fatigue noted early and reduce or eliminate weakness depending on the frequency of stimulation.