Some of the adverse effects of lead (Pb) may be associated with oxidative damage of lipids, proteins or DNA. In a previous study a linkage was observed between the susceptibilities of waterfowl species to Pb poisoning with oxidative stress. To investigate this relationship among the individuals of a single species, four groups of 12 mallards were fed for three weeks diets containing high or low levels of vitamin E (20 or 220 UI/kg) and high or low levels of Pb (0 or 2 g/kg). During the first week of Pb exposure, mallards developed hemolytic anemia, and during the second week, signs of neurological impairment. Histological findings in the Pb exposed mallards were hemosiderosis, demyelinization of sciatic and brachial nerves, and tumefaction of renal tubular epithelium with the presence of intranuclear inclusion bodies. Lipid peroxidation increased with Pb exposure in blood, liver, bile and brain, but decreased in nerves. Glutathione (GSH) increased with Pb exposure in liver and bile, and its oxidized/reduced ratio only increased in bile. Pb exposure inhibited GSH peroxidase activity (GPX) in plasma, liver and brain, and decreased protein thiols (PSH) in blood and liver. Vitamin E significantly prevented lipid peroxidation in nerves, but did not alleviate any sign of Pb poisoning. Pb-induced pathological changes associated with hepatic and nervous functions were significantly correlated with lower GPX activity and PSH concentrations in these tissues rather than lipid peroxidation. Data suggest that inhibition of antioxidant enzymes and interaction with sulfhydryl groups of proteins may play a more important role in Pb poisoning of waterfowl than lipid peroxidation.