AIM: As an immune-modulating agent, levamisole has been reported to stimulate depressed T-cell activity, enhance B lymphocyte function and restore delayed hypersensitivity reactions in immune-depressed patients. There are a number of recent studies claiming that levamisole can improve response rate to hepatitis B virus (HBV) vaccination in haemodialysis patients. The present study has examined this hypothesis amongst some Iranian patients, using double-blind randomized clinical trial. METHODS: During a 12 month period, 70 patients on maintenance haemodialysis with negative anti-hepatitis B surface antibody (HBsAb) and HBV core antibody (HBcAb), from four different dialysis centres were enrolled into the study. The patients were randomized to two groups. The first group (levamisole group) received 40 microg doses of recombinant HBV vaccine i.m. at 0, 1 and 6 months, plus 100 mg levamisole p.o., after each haemodialysis session. The second group (placebo group) received the same vaccination protocol, except for the placebo instead of levamisole. The patients were followed on serum HBsAb level. Those with an HBsAb level of above 10 mIU/mL, 1 month after the third dose of vaccination, were considered as responders. RESULTS: The levamisole group was comprised of 38 patients and the placebo group of 32 patients. Thirty-one patients (81.6%) of levamisole group and 26 patients (81.3%) of placebo group responded to vaccination. The difference between two groups was not significant. CONCLUSION: This study indicated that in a haemodialysis population with high response to HBV vaccination, levamisole might have no significant effect in enhancing the response. Further studies with higher power can give more accurate results.