Uncontrolled lipid peroxidation may play an important role in the pathophysiology of preeclampsia by causing vascular endothelial cell dysfunction. Sera contain antioxidant mechanisms that serve to control lipid peroxidation. We tested the hypothesis that the sera antioxidant protective mechanisms are diminished in women with preeclampsia. Blood samples were collected within 24 hours of delivery (pre-delivery) and by 24 hours postpartum (post-delivery) from women with preeclampsia (N = 8) and from matched controls with uncomplicated pregnancies (N = 8). Antioxidant activity was determined by the ability of sera to inhibit autoxidation of a standardized brain homogenate. Lipid peroxidation of both brain homogenate and sera was analyzed by high-pressure liquid chromatography using the amount of malondialdehyde present as an indicator of peroxidation. Pre-delivery sera from women with preeclamptic pregnancies had one-half the antioxidant activity of sera from women with uncomplicated pregnancies (42 versus 90%; P less than .01). Malondialdehyde values alone were not significantly different between the groups in either the pre-delivery or post-delivery samples. When using a ratio to evaluate the relative balance between lipid peroxidation and antioxidant activity, pre-delivery samples from women with preeclampsia had over a twofold increase in this ratio compared with samples from uncomplicated pregnancies. In conclusion, in contrast to women with uncomplicated pregnancies, women with preeclampsia have antioxidant activity that is markedly reduced by late gestation. For women with preeclampsia, this may result in a greater potential for endothelial oxidative damage.