The antioxidant effects of 17beta-estradiol, its main A- and D-ring metabolites, and of vitamin E were compared in vitro. Low density lipoprotein (LDL) was isolated from fresh human blood, and LDL oxidation was evaluated spectrometrically by monitoring diene formation of fatty acids. All substances tested exhibited antioxidant potential. The A-ring metabolites (catecholestrogens) emerged as more potent inhibitors of LDL oxidation than the parent substance estradiol, its D-ring metabolites, and vitamin E. Since oxidized LDL seems to play a crucial role in the development of atherosclerosis, its inhibition may be of preventive value. In summary, A-ring metabolites of estradiol (catecholestrogens), substances that occur naturally in the body, may be involved in the physiologic inhibition of LDL oxidation.