Owing to the presence of hemoglobin and polyunsaturated fatty acids, erythrocytes are a convenient model to understand membrane oxidative damage induced by various xenobiotic pro-oxidants. This study investigated the antioxidant activity of vanillin, a naturally occurring food-flavoring agent, against carbon tetrachloride (CCl(4))-induced erythrocyte damages in Wistar albino rats. A single injection of CCl(4) (1 ml/kg, intraperitoneally [i.p.]) caused a significant induction of oxidative damage as evidenced by increased thiobarbituric acid reactive substances, protein carbonyl levels and osmotic fragility accompanied with a significant decrease in Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities. Furthermore, catalase and superoxide dismutase activities were significantly elevated, while glutathione levels, glutathione-S-transferase and glutathione peroxidase activities were markedly reduced in the erythrocytes of CCl(4)-treated rats. Pretreatment of rats with vanillin (150 mg/kg/day, i.p.) for 3 consecutive days before CCl(4) injection protected erythrocytes against the increase of lipid peroxidation and degradation of membrane proteins compared to CCl(4)-treated rats and exhibited marked prevention against CCl(4)-induced oxidative stress, alterations of membrane-bound enzymes as well as erythrocyte osmotic fragility. Our results suggest that vanillin plays a protective and curative role against the harmful effects of CCl(4) on erythrocytes, thus ensuring membrane cell integrity.