AIM: Severe uveitis is potentially associated with visual impairment or blindness in young patients. Therapeutic strategies remain controversial. The efficacy of interferon alpha-2a (IFN-alpha2a) in severe uveitis, refractory to steroids and conventional immunosuppressive agents, was evaluated. PATIENTS AND METHODS: Patients were included after a major relapse of uveitis following corticosteroids and immunosuppressants. IFN-alpha2a (3 million units three times a week) was administered subcutaneously. Efficacy was assessed by improvement in visual acuity, decrease in vitreous haze, resolution of retinal vasculitis and macular oedema, assessed by fundus examination and fluorescein angiography, and decrease in oral prednisone threshold. RESULTS: 45 patients were included. Median age was 32.3 years (range 8-58) and sex ratio (F/M) was 0.66. Uveitis was associated with Behçet's disease in 23 cases (51.1%) and with other entities in 22 cases (48.9%). Median duration of uveitis before interferon therapy was 34.9 months (range 3.4-168.7) and an average of 3.26 relapses following corticosteroids and immunosuppressants was noted. Uveitis was controlled in 82.6% of patients with Behçet's disease and 59% of patients with other types of uveitis (p = 0.07). During a mean follow-up of 29.6 months (range 14-55), median oral prednisone threshold decreased significantly from 23.6 mg/day (range 16-45) to 10 mg/d (range 4-14) (p<0.001). Interferon was discontinued in 10 patients (22.2%) with Behçet's disease and in four patients without Behçet's disease. Relapses occurred in four and one cases, respectively. CONCLUSIONS: Interferon therapy appears to be an efficient strategy in severe and relapsing forms of Behçet's disease but also in other uveitic entities. However, it seems to act more to suspend rather than cure the disease. Therefore, IFN-alpha2a may be proposed as a secondline strategy after failure of conventional immunosuppressants.