OBJECTIVE: To test the efficacy of systemic interferon alpha 2b (IFN alpha 2b) treatment in the mucocutaneous and joint symptoms of Behçet's syndrome. METHODS: The 48-week open, self-controlled trial was conducted in 3 phases. After the pretreatment phase of 16 weeks, 20 patients (8 men, 12 women; mean age 37 +/- 7 years SD) were treated with IFN-alpha 2b at a dose of 5 million units 3 times a week for 6 weeks followed by 5 million units once a week for 10 weeks. The subsequent 16 weeks not taking the medication was the posttreatment phase. RESULTS: Treatment with IFN-alpha 2b significantly reduced the mean number of arthritis attacks (F = 3.48; p < 0.05), their mean duration (F = 3.77; p < 0.05), and the mean erythrocyte sedimentation rate (F = 6.66; p < 0.001). The mean number of mucocutaneous lesions also showed a decrease, but this was not statistically significant. Except for the duration of arthritis, the mean number and frequency of all symptoms tended to return to pretreatment levels in the posttreatment phase. CONCLUSION: This pilot study shows that systemic IFN may be effective in the treatment of arthritis of Behçet's syndrome.