Background: Variable effectiveness of high dose cimetidine therapy for multiple warts, verruca plana and molluscum contagiosum has been reported. The immunomodulatory actions of cimetidine, an H2-receptor antagonist, and its use in the treatment of viral warts have been described previously but its effectiveness is still debated. Objective: The purpose of this study is to evaluate the efficacy and safety of high dose cimetidine therapy for periungual warts. Methods: Twenty seven patients with periungual warts were treated with high dose oral cimetidine (30∼40 mg/kg/ day). Results: Evaluable data was obtained in 20 (male 10, female 10) of the 27 patients enrolled in the study. 19 patients (95% of 20 patients) showed either complete resolution (50% of 20 patients) or partial resolution (45% of 20 patients) of their periungual warts without any side effect. Conclusion: Unlike aggressive therapies, oral high dose cimetidine administration is simple and cost effective and does not usually interfere with the patient`s work activity or affect his or her social life. Though we can consider that high dose cimetidine therapy is one of the effective therapy for periungual warts, complete remission rate is not so high. Combined therapy with other topical therapy using liquid nitrogen, formic acid, silver nitrate or imiquimod, etc. would also be considered and evaluated for more effective treatment of periungual warts. (Korean J Dermatol 2007;45(12):1258∼1264)