Although the precise mechanisms underlying the dysfunction of sarcoplasmic reticulum(SR) that occurs during skeletal muscle fatigue remain obscure, it has been hypothesized that it may be attributable to oxidation of critical sulfhydryl groups residing in SR Ca^-ATPase protein by endogenously produced reactive oxygen species. In order to test this hypothesis, SR Ca^-ATPase activities in the absence or presence of the disulfide reducing agent, dithiothreitol(DTT), were examined in muscle homogenates of the soleus muscles(SOL) and the superficial portions of the vastus lateralis muscles(VS) from the rat subjected to exhaustive running at 50 m/min on a 10% grade. Immediately after exercise, the catalytic activity of SR Ca^-ATPase was significa...