Lipid peroxidation which can be measured indirectly by erythrocyte osmotic fragility is a molecular mechanism implicated in chlorpyrifos poisoning. The aim of the present study was to evaluate the comparative effects of vitamin C and acetyl-L-carnitine on subacute CPF-induced erythrocyte osmotic fragility in Wistar rats. Forty-nine adult male Wistar rats divided into 7 groups of 7 animals each were used as experimental subjects. Rats in groups I (S/oil), II (VC), III (ALC) and IV (CPF) were exposed to soya oil only (2 ml/kg), vitamin C (100 mg/kg), acetyl-Lcarnitine (300 mg/kg) and chlorpyrifos only (8.5 mg/kg~ 1/10th of the LD50), respectively. Groups V (VC+CPF) and VI (ALC+CPF) were pretreated with vitamin C (100 mg/kg) and acetyl-Lcarnitine (300 mg/kg), respectively, and then dosed with CPF (8.5 mg/kg) 30 min later. While group VII (VC+ALC+CPF) was pretreated with the combination of VC (100 mg/kg) and ALC (300 mg/kg) and then dosed with CPF (8.5 mg/kg), 30 min later. These regimens were administered orally once daily for a period of 28 days. At the end of the study, the rats were sacrificed and erythrocyte analyzed for erythrocyte osmotic fragility. The study showed that subacute CPF exposure caused increase in erythrocyte osmotic fragility, which was significantly decreased (P <0.05) by vitamin C, but differentially decreased (P >0.05) by ALC and the combination of VC and ALC. In conclusion, the study showed that CPF-evoked erythrocyte fragility was best ameliorated by pretreatment with vitamin C alone.