OBJECTIVE To evaluate the efficacy and safety of systemic interferon alfa treatment in patients with Adamantiades-Behçet disease. METHODS Reports and abstracts published in 1986 through 1997 in all languages were identified by the MEDLINE database, the Reference Index Related to Behcet's Disease, the Behçet disease conference proceedings, and abstract booklets. The indexing terms used Behçet and interferon. METHODS Twenty-two reports identified were included to estimate the efficacy of interferon alfa on mucocutaneous, ocular, and joint manifestations. Responses of individual mucocutaneous signs were evaluated in 8 reports. Adverse effects were sufficiently documented in 12 reports. All patients met the criteria of the Behçet Syndrome Research Committee of Japan or those of the International Study Group for Behçet's Disease. METHODS Data were extracted and evaluated according to the following criteria: complete remission, disappearance of all manifestations during treatment; partial remission, greater than 50% decrease in the number, severity, duration and/or frequency of recurrence of the lesions; stable disease, less than 50% change in the manifestations; and progressive disease, greater than 50% deterioration of existing manifestations or/and the development of new ones. RESULTS Systemic interferon alfa has been administered in 144 patients with Adamantiades-Behçet disease by subcutaneous or intramuscular injections of 3 to 18 x 10(6) units of interferon alfa-2a (70 patients) or 3 to 5 x 10(6) units of interferon alfa-2b (74 patients) daily or 3 times per week for 1 to 60 months. Seventy-four percent (92/124) of patients with mucocutaneous manifestations, 95% (37/39) of patients with uveitis, and 93% (51/55) of patients with arthropathy/arthritis exhibited a partial or complete response. Interferon alfa-2a regimens were more effective than interferon alfa-2b ones on mucocutaneous (47% vs 7% complete response) and ocular (67% vs 8% complete response; P < .001) manifestations. Mucocutaneous and ocular manifestations responded within 1 to 4 months after initiation of therapy. Thirty-eight percent (20/52) of patients with mucocutaneous lesions, 73% (8/11) of patients with uveitis, and 88% (21/24) of patients with arthropathy/arthritis experienced recurrences immediately or up to 7 months after discontinuation of treatment. Mild adverse effects were generally recorded; transient influenza-like symptoms (87% vs 63%; P < .05) and reversible leukopenia (24% vs 4%; P < .05) occurred more often under interferon alfa-2a regimens, while reversible mild alopecia was more common in patients receiving interferon alfa-2b (2% vs 28%; P < .01). CONCLUSIONS Systemic interferon alfa treatment is reasonable for Adamantiades-Behçet disease. A 3-month high-dose regimen (9 x 10(6) units 3 times per week) followed by a low maintenance dose (3 x 10(6) units 3 times per week) is recommended.