The activities of superoxide dismutase, catalase and glutathione reductase were not affected byin vitroincubation with the intracellular proteinase calpain, suggesting that these enzymes are notin vivosubstrates of calpain. In contrast, the activity of another important antioxidant enzyme, glutathione peroxidase, is stimulatedin vitroby calpain. This may explain the correlation between elevations in glutathione peroxidase activity and calpain activity which occur in aging, exercised and dystrophic muscle. Calpain treatmentin vitrocaused a large decrease in the activity of carnosine synthetase which is involved in the synthesis of the putative antioxidant carnosine. This may be the reason for thein vivocorrelation between elevated calpain and diminished carnosine levels in aging, hypertensive, denervated and dystrophic muscles.