The purposes of these experiments were to compare the activities of glucose 6-phosphate dehydrogenase (G6PDH) and the lysosomal enzyme N-acetyl-beta-glucosaminidase (NAG) in rat muscles and to assess protein degradation after eccentric exercise (running down a 18 degrees grade). The following results were obtained: (1) Muscles in which the G6PDH activity was increased also showed an increase in NAG activity that was smaller and occurred later and/or was more prolonged than the increase in G6PDH activity. (2) The urinary 3-methylhistidine/creatinine ratio was statistically elevated for 3 days after eccentric exercise and this increase was much larger and more prolonged than previously observed in rats run on the level. Taken together our results suggest that increased protein degradation after exercise is due to increased proteolysis of muscle tissue damaged during the exercise bout and that lysosomal enzymes may be involved in this degradation.