Adriamycin elicited a stimulation of rat central nervous system lipid peroxidation, both in vivo and in vitro, as evidenced by the increase in the content of thiobarbituric acid reactants, which was found to be NADPH-dependent. The antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were seen to decrease on exposure to adriamycin (1 mg/kg for a period of 7 days), together with a significant decrement in the GSH/GSSG ratio, thus contributing to the oxidative insult to the tissue. The in vitro addition of GSH or vitamin E to brain homogenates offered protection against adriamycin-induced lipid peroxidation, suggesting that supplementation with these antioxidants could improve the therapeutic value of the drug.