Both, developmental lead (Pb) exposure and ethanol intake induce reactive oxygen species (ROS), thus modifying the activity of antioxidant enzymes such as catalase -CAT, superoxide dismutase -SOD, and glutathione peroxidase -GPx. Importantly, CAT is also implicated in ethanol?s brain oxidation to acetaldehyde. Based on these evidences, the aim of this study was to evaluate whether perinatal low-level Pb exposure would modify the activity of these enzymes in male Wistar rats that have voluntarily consumed ethanol. Briefly, 35 day-old rats exposed to water or 220 ppm Pb during gestation and lactation were presented 2h daily with increasing ethanol solutions (2-10%), and water until postnatal day 63 (group 63d ETOH). Another two groups were included: 35d non-ETOH, and 63d non-ETOH. At the end of the experiment, all animals were sacrificed, blood, and liver removed to determine the activity of the antioxidant enzymes above-mentioned. All three enzymes (CAT, SOD and GPx) were increased in blood selectively in the 35d non-ETOH group perinatally exposed to Pb, whereas only CAT was further increased in the 63d ETOH Pb-exposed group. On the other side, liver SOD activity was decreased in the 35d non-ETOH and 63d non-ETOH Pb-exposed groups, whereas liver CAT activity was reduced in the 63d ETOH and 63d non-ETOH Pb-exposed groups. No changes were observed in liver GPx activity. These results suggest differential antioxidant enzymatic activity probably determined by the dynamic Pb toxicokinetics in blood and soft tissue, with CAT playing a critical role in the Pb/ethanol interaction.