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We report a two- to three-fold increase in free radical (R^•) concentrations of muscle and liver following exercise to exhaustion. Exhaustive exercise also resulted in decreased mitochondrial respiratory control, loss of sarcoplasmic reticulum (SR) and endoplasmic reticulum (ER) integrity, and increased levels of lipid peroxidation products. Free radical concentrations, lipid peroxidation, and SR, ER, and mitochondrial damage were similar in exercise exhausted control animals and non-exercised vitamin E deficient animals, suggesting the possibility of a common R^• dependent damage process. In agreement with previous work showing that exercise endurance capacity is largely determined by the functional mitochondrial content of muscle (1–4), vitamin E deficient animals endurance was 40% lower than that of controls. The results suggest that R^• induced damage may provide a stimulus to the mitochondrial …