Major alterations in the structure and function of the sarcoplasmic reticulum (SR) occur following strenuous exercise. Gross focal dilation of the SR is accompanied by a depression in the rate of calcium (Ca2+) uptake, a diminished Ca2+ release, and an increase in the intracellular free calcium concentration ([Ca2+]f). This failure in Ca2+ regulation by the SR may result in activation of Ca(2+)-sensitive compounds that are involved in muscle autolysis. These compounds include proteases and phospholipases known to act on fibrillar membranes and proteins. The mechanisms responsible for the alterations in SR structure and function are unknown; however, changes in muscle pH, high energy phosphates, ionic balance, or temperature are known to have detrimental effects on SR function.