Various immunomodulating agents have been used in the treatment of recalcitrant warts, but none is uniformly effective. Aggressive surgical therapy of warts in children is painful and may require general anesthesia. Drugs such as cimetidine and levamisole have been tried with varying success rates. Given the different target of activities of immunomodulation by cimetidine and levamisole, we questioned whether the combination might be more effective and conducted a double-blind comparative trial of a combination of cimetidine and levamisole versus cimetidine alone. Forty-four patients with multiple recalcitrant warts were assigned to one of two treatment groups (groups A and B) in double-blind fashion. Of the 44 patients, 19 in group A and 20 in group B could be evaluated. At the end of therapy, cure rates (complete clearance) obtained were 31.5% of those in group A and 65% of those in group B (combination treatment). A statistically significant improvement was seen in patients treated with the combination of levamisole and cimetidine (p=0.0150). The rate of regression was faster in group B (average regression period of 7.8 weeks compared with 11 weeks in group A). The present study demonstrated that the combination of cimetidine with levamisole is more effective than cimetidine alone and is a highly effective therapy for the treatment of recalcitrant warts.