Various immunomodulating agents have been used in the treatment of recalcitrant warts, but none is uniformly effective. Drugs like cimetidine and levamisole have been tried with varying success rates. Given the different target activities of immunomodulation by levamisole and cimetidine, we questioned whether the combination might be more effective and conducted this double-blind comparative trial of a combination of cimetidine and levamisole versus cimetidine alone. Forty-eight patients with multiple recalcitrant warts were assigned to two treatment groups (A and B) in double-blind fashion. Of the 48 patients, 22 in group A and 21 in group B were able to be evaluated. At the end of therapy, cure rates obtained were 45.5% (10/21) in cimetidine treated patients (group A) and 85.7% (18/21) in combination treated patients (group B). A statistically significant improvement was seen in patients treated with the combination of levamisole and cimetidine (P < 0.01). A similar statistically significant result was obtained on using intention to treat analysis (P < 0.02). The rate of regression was faster in group B (average regression period of 7 weeks compared with 10 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.