The antioxidant activities of 17-beta-estradiol (E2) and other steroid hormones were studied by determining their effect on copper-catalyzed (cell-free) and mononuclear cell-mediated oxidation of low-density lipoproteins (LDL), as measured by the production of thiobarbituric acid-reactive substances (TBARS). The oxidation of LDL increased linearly with copper concentrations ranging from 0 to 10 mumol/L. E2 at a concentration of 1 mumol/L inhibited LDL oxidation by 37% to 62% at the various concentrations of copper. In a time-course study, E2 at 1 mumol/L delayed the onset of LDL oxidation in the presence of 5 mumol/L copper. E2 (1 mumol/L) inhibited TBARS production catalyzed by 5 mumol/L copper by 54%, compared with 60% inhibition by 1 mumol/L butylated hydroxytoluene (BHT), a known inhibitor of lipid peroxidation. Estriol at 5 mumol/L decreased LDL oxidation by 49%. Dehydroepiandrosterone (DHEA), testosterone, and estrone had no significant effects. E2 was also an effective inhibitor of mononuclear cell (MNC)-mediated oxidation of LDL, but had no effect on superoxide production by these cells. The onset of TBARS formation from cell-mediated LDL oxidation was also delayed by incubation with 1 mumol/L E2. The results indicate that estrogen may protect against atherosclerosis by inhibiting lipoprotein oxidation.