Glutathione status and products from lipid peroxidation [measured as thiobarbituric acid reactive substances (TBARS)] were determined in red and white muscle tissue of the rat. Marked differences between both muscle types were found in reduced glutathione (GSH) and oxidized glutathione (GSSG) content, exhibiting 163% and 183%, respectively, higher levels in red than in white muscle tissue, while the ratio of GSSG/GSH showed no differences. These characteristics may be due to an adaptive mechanism related to the 48% higher baseline level of TBARS in red muscle tissue. Immediately after 4 h of tourniquet-ischemia GSH, GSSG, and TBARS were increased (16%, 32%, 45% in white muscle; 19%, 49%, and 42% in red muscle, respectively), whereas the GSSG/GSH ratio remained unchanged. During the subsequent reperfusion period, GSH decreased within 2 h by 39% in white and 89% in red muscle to a minimal level of 5 mmol/g protein in both types of muscle. No recovery from the depletion was observed up to 12 h of reperfusion. The GSH decrease was parallelled by a marked increase of the GSSG/GSH ratio (150% in white and 450% in red muscle) and followed by about 150% increase in TBARS in both muscle types. This suggests that the increase in damaging TBARS is a secondary event after depletion of cellular antioxidants. Treatment of the animals during the reperfusion period with methyl-prednisolone, deferoxamine, or superoxide dismutase and catalase did not prevent the GSH decrease, but were effective in reducing the GSSG/GSH ratio to near normal and reducing the TBARS increase by about 50%.