Studying the responsiveness of specific CNS pathways to electrical or magnetic stimulation can provide important information regarding fatigue processes in the central nervous system. In this study, we investigated the changes in corticospinal responsiveness during a sustained submaximal contraction of the triceps surae. Comparisons were made between the size of motor evoked potentials (MEPs) elicited by motor cortical stimulation and cervicomedullary motor evoked potentials (CMEPs) elicited via magnetic stimulation of the descending tracts, in order to determine the site of any change in corticospinal responsiveness. Participants maintained an isometric contraction of triceps surae at 30% of maximum voluntary contraction (MVC) for as long as possible on two occasions. Stimulation was applied either to the motor cortex or to the cervicomedullary junction every minute during contraction until task failure. Peripheral nerve stimulation was also applied to evoke maximal M-waves (M_max) and a superimposed twitch. Additionally, MEPs and CMEPs were evoked during brief contractions at 80, 90 and 100% MVC as a non-fatigue control. During the sustained contractions, MEP size increased significantly in both soleus (113%; SOL) and medial gastrocnemius (108%; MG) and at task failure matched MEP size in the pre-fatigue MVC (~20-25% M_max). In contrast, CMEP size increased significantly in MG (51%) but not in SOL (63%), and at task failure was significantly smaller than during pre-fatigue MVC (5-6% M_max versus 11-13% M_max). The data indicate that cortical processes contribute substantially to the increase in corticospinal responsiveness observed during sustained submaximal contraction of triceps surae.