Hill, EC, Housh, TJ, Smith, CM, Schmidt, RJ, and Johnson, GO. Gender- and muscle-specific responses during fatiguing exercise. J Strength Cond Res 32(5): 1471–1478, 2018—The purpose of the present investigation was to examine potential gender-related differences in electromyographic (EMG) and mechanomyographic (MMG) responses during submaximal, concentric, isokinetic, forearm flexion muscle contractions. Twelve men and 12 women performed concentric peak torque trials before (pretest) and after (posttest) a fatiguing exercise bout that consisted of 50 submaximal (65% of concentric peak torque), concentric, isokinetic (60°·s−1), forearm flexion muscle contractions. Surface EMG and MMG signals were simultaneously recorded from the biceps brachii and brachioradialis muscles. There was a gender-related difference in the decline in absolute concentric peak torque for the men (23.8%) vs. women (18.5%) that was eliminated when covaried for differences in pretest concentric peak torque values. During the fatiguing exercise bout, EMG amplitude(AMP) increased and EMG mean power frequency (MPF) decreased for both genders and muscles. There were, however, muscle- and gender-specific increases, decreases, and no changes for MMG AMP and MMG MPF. The gender-related difference for the posttest decline in concentric peak torque was associated with differences in muscle strength which may have resulted in greater blood flow occlusion in the men than the women. The muscles with the most pronounced fatigue-induced neuromuscular responses were the biceps brachii in men and the brachioradialis in women. These findings may be related to gender differences in the usage patterns of synergistic muscles during a fatiguing task.