This study aimed to investigate central and peripheral contributions to fatigue during repeated maximal voluntary isometric plantar flexions (MVCs). Changes in joint torque, level of activation (LOA), resting twitch amplitude (RT), electromyographic signals (EMG), and presynaptic inhibition of Ia afferents were investigated during 9 bouts of 10 MVCs. MVCs lasted for 2 s and were separated by 1 s. The interval between bouts was 10 s. Electrical stimulation was applied to the tibial nerve; at rest to evoke RTs, M waves, and two (1.5-s interval) H reflexes; with the soleus EMG at 30% of that during MVC to evoke M waves and two H reflexes; and during MVCs to measure LOA. Over the nine bouts, LOA decreased by 12.6% and RT by 16.2%. EMG root mean square during MVCs remained unchanged for the soleus and tibialis anterior muscles, but it decreased for medial gastrocnemius. Peripheral fatigue (decrease in RT) was positively correlated to LOA, whereas central fatigue (decrease in LOA) was not. Depression of both H reflexes suggests that presynaptic inhibition after the first bout was partly induced by homosynaptic postactivation depression of the Ia terminal. The H-reflex-to-M-wave ratio increased with fatigue in both passive and active states, with no change in the ratio of the second H reflex to the first, thereby indicating a decrease of presynaptic inhibition during fatigue. The results indicate that both central and peripheral mechanisms contributed to the fatigue observed during repeated MVCs and that the development of peripheral fatigue was influenced by the level of voluntary activation and initial plantar flexor torque.