This study was aimed to examine the effects of a single high dose of natural and synthetic estrogens on the antioxidant defense enzymes in liver and blood. Female Wistar albino rats, four to six months old, were divided into three groups, and received either i.p. injections of diethylstilbestrol (DES; 150 mg kg(-1) b.w.) or s.c. injections of estradiol (E-2; 25 mg kg(-1) b.w.), and the third group (control) was injected the solvent. Animals were killed under light ether anesthesia three hours after injection. Cu-Zn superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (Cat) enzyme activities and fluorometric malondialdehyde (MDA) determination were performed in liver tissue homogenates and in blood. Acute estradiol injection caused a significant increase in both MDA levels and GPx activity in liver tissue when compared to the controls, (p < 0.05 and p < 0.02; respectively). Changes in both enzyme activities and MDA concentration were unremarkable following acute DES injection. In blood, only Cu-Zn SOD activity was significantly altered in blood following E-2 injection. Although the significance of alteration in GPx activity remains unclear, it is most likely related to enhanced generation of lipoperoxides. A significant increase in MDA concentrations in liver tissue is indicative of pro-oxidative damage rather than an antioxidant action by E-2.