The ability of melatonin to protect against paraquat-induced oxidative damage in rat lung, liver, and serum was examined. Changes in the levels of malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HDA) and reduced and oxidized glutathione concentrations were measured. Paraquat (50 mg/kg) was injected i.p. into either Sprague-Dawley or Wistar rats with or without the co-administration of 5 mg/kg melatonin. Paraquat alone increased MDA + 4-HDA levels in serum and lungs of both rat strains, with these increases being abolished by melatonin co-treatment. Paraquat also decreased reduced glutathione levels and increased oxidized glutathione concentrations in lung and liver; these changes were negated by melatonin. The effect of melatonin on paraquat-induced mortality was also studied. Paraquat at a dose of 79 mg/kg was lethal for 50% of animals within 24 hr; when administered together with melatonin, the LD50 for paraquat increased to 251 mg/kg.