Reactive oxygen species (ROS) may he involved in the toxicity of chlorpyrifos-ethyl (CE) [O, O-diethyl-O-(3,5,6-trichloro-2-pyridyl)phosphorothioate]. We have: therefore, examined the in vivo effects of CE on the rat erythrocyte antioxidant system and evaluated the ameliorating effects of melatonin and a combination of vitamin E and vitamin C on the oxidative damage induced by CE. The experimental groups were: (1) control group, (2) CE-treated group (CE); (3) vitamin E plus vitamin C treatment group (Vit) (4) melatonin-treated group (Mel), (5) vitamin E plus; vitamin C: plus CE treatment group (Vit + CE), and (6) melatonin plus CE treatment group (Mel + CE). Vitamin E and vitamin L were administered intramuscularly once a day for 6 consecutive days at 150 and 200 mg/kg, respectively, in the Vit and Vit + CE groups. Melatonin was administered intramuscularly at 10 mg/kg pet day for 6 consecutive days in the Mel and Mel + CE groups. At the end of the fifth day, the rats of CE. Vit + CE and Mel a CE groups were treated orally with the first of two equal doses of 41 mg/kg CE, the second oral dose being given 21 h later. Blood samples were taken 24 h after the first CE administration. Levels of thiobarbituric acid reactive substance (TBARS), antioxidant defence potential (AOP), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were determined in erythrocytes. In comparison with the control group, oral administration of CE significantly (P < 0.05) stimulated TEARS activity while significantly (P < 0.05) inhibiting AOP and the activities of SOD and CAT. However. GSH-Ps activity remained unchanged by CE treatment, Treatment with melatonin and vitamins E plus C significantly (P < 0.05) reduced the CE-induced increase of TEARS, and overcame the inhibitory effect of CE on SOD and CA-P, but not on AOP. Melatonin treatment significantly (P < 0.05) increased only GSH-Px activity, il respective of the effect of CE. These results suggest that CE treatment increases in vivo lipid peroxidation and decreases antioxidant defence by increasing oxidative stress in erythrocytes of rats, and melatonin and a combination of vitamin and vitamin C can reduce this lipooperoxidative effect.