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Cigarette smoking is common in societies worldwide and has been identified as injurious to human health. Human red blood cells are important targets for electrophilic and oxidant foreign compounds. In the present study, the possible role of antioxidant status on smoking-induced erythrocyte hemolysis of smokers was studied. Erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, reduced glutathione (GSH) level, erythrocyte membrane lipid peroxidation, total cholesterol and phospholipids were determined. Further, nitrite/nitrate levels (NO(2)/NO(3)) in both plasma and erythrocyte lysate were measured. Results showed increased plasma and erythrocyte membrane lipid peroxidation and nitrite/nitrate levels in smokers. The activities of SOD, CAT and GPx were also increased with reduced glutathione (GSH) level in smokers. No significant change was observed in smokers red cell hemolysis and cholesterol/phospholipid (C/P) ratio compared to controls. Erythrocyte membrane lipid peroxidation was positively correlated with SOD (r = 0.482, p < 0.01) and GPx (r = 0.368, p < 0.018) in smokers. Increased levels of nitrite/nitrate and antioxidant status of erythrocytes might be playing a crucial role in protecting red cell from free radical damage induced by cigarette smoke.