This study was undertaken to compare placental levels of 2,3-Dioxygenase (IDO), a free radical scavenger, and 4-Hydroxynonenal (4-HNE), a major by-product of lipid peroxidation, in normal and pre-eclamptic pregnancies. Placentae were collected at caesarean section from women with a term, normal singleton pregnancy (37-40 weeks' gestation, n=10) and women with a term singleton pregnancy complicated by pre-eclampsia (n=10). IDO and 4-HNE localization and intensity was studied by semi-quantitative immunohistochemistry and differences between groups were analysed using the Mann-Whitney U test. Immunostaining for IDO was located primarily in endothelial cell nuclei, with a reduced level of staining in the cytoplasm, in most capillaries from all placentae examined. A significantly higher level of IDO immunostaining was observed in normal placentae compared to pre-eclamptic placentae (P=0.008). 4-HNE was located mainly in the cytoplasm of syncytiotrophoblast cells of all placentae examined. There were no significant differences in the pattern or intensity of 4-HNE immunostaining levels between normal and pre-eclamptic pregnancies (P=0.684). Our IDO results support the hypothesis of decreased anti-oxidative capability in the placenta and the possibility of an ineffective compensatory mechanism against increased oxidative stress in the fetus.