Physical exercise at submaximal levels in rats results in a progressive depletion of liver glutathione to about 20% of the levels found in sedentary controls which persists for several hours following the cessation of exercise. Skeletal muscle appears to be spared this severe depletion phenomenon. The levels of plasma glutathione show a transient increase at the beginning of the exercise bout followed by a linear decrease with increased running time of the animals. These results may be particularly relevant when attempting to understand the effects of physical exercise on a large number of cellular and organismal functions that are known or suspected to depend critically on the glutathione status of the liver.