The effects of organophosphate insecticide methidathion (MD) on lipid peroxidation and anti-oxidant enzymes and the ameliorating effects of a combination of vitamins E and C against MD toxicity were evaluated in rat erythrocytes. Experimental groups were: control group, MD-treated group (MD), and MD + vitamin E + vitamin C-treated group (MD + Vit). MD and MD + Vit groups were treated orally with a single dose of 8 mg/kg MD body weight at 0 hour. Vitamins E and C were injected at doses of 150 mg/kg body weight, i.m. and 200 mg/kg body weight, i.p., respectively, 30 min after the treatment of MD in the MD + Vit group. Blood samples were taken 24 hours after the MD administration. The level of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD), glutathione peroxidese (GSH-Px), and catalase (CAT) were studied in the erythrocytes. MDA level increased significantly in the MD group compared to the control group (P < 0.05) and decreased significantly in the MD + Vit group compared to the MD group (P < 0.05). The activities of SOD, GSH-Px, and CAT decreased in the MD group compared to the control group (P < 0.05). Only GSH-Px activity increased in the MD + Vit group compared with the MD group. These results suggest that treating rats with MD increases LPO and decreases anti-oxidant enzyme activities in erythrocytes. Furthermore, single-dose treatment with a combination of vitamins E and C 30 min after the administration of MD can reduce LPO caused by MD.