Background: There is no definite treatment for Behcet's disease. New drugs are being evaluated in cases unresponsive to conventional treatment modalities. Objective: In this study we investigated the efficacy of interferon alfa-2a on skin lesions in 18 Behcet's disease patients who had predominantly mucocutaneous involvement. Methods: Eighteen patients with Behcet's disease were treated with interferon alfa-2a at 3 million IU/day in the first week (three times a week), 6 million IU/day in the second week (three times a week), 9 million IU/day in the third week and thereafter (three times a week), Interferon alfa-2a was administered subcutaneously for a total of 12 weeks, Results: At the end of the treatment the efficacy of the drug was found to be good in 9 patients and very good in 7 patients, Interferon alfa-2a is particularly effective in skin manifestations such as genital ulceration and erythema-nodosum-like lesions. It was also found to be effective in systemic manifestations such as fever, diarrhea and eye involvement. Conclusion: Our results indicate that interferon alfa-2a is a promising drug in the treatment of Behcet's disease.