BACKGROUND Severe episodes of steroid-refractory ulcerative colitis (UC) were considered an indication for surgery until the introduction of new immunosuppressive agents such as cyclosporine. OBJECTIVE 1) To confirm the efficacy of intravenous cyclosporine in inducing remission in severe episodes of steroid-refractory UC; 2) To analyze the efficacy of triple immunosuppressive therapy with cyclosporine, azathioprine and prednisone in the maintenance of remission induced by intravenous cyclosporine. METHODS Fourteen patients diagnosed with a severe episode of steroid-refractory UC were treated with intravenous cyclosporine at a dose of 4 mg/kg/day. In all patients, after response was induced, this regimen was substituted by oral cyclosporine plus azathioprine at a dose of 2-2.5 mg/kg/day and decreasing doses of corticoids. Neoral cyclosporine was progressively reduced until discontinuation within 3 months, coinciding with a simultaneous decrease of oral steroids. RESULTS All patients showed response to intravenous cyclosporine with a significant reduction in the Truelove index calculated before and after treatment. After remission was induced, all patients followed triple immunosuppressive therapy for 3 months. In the follow-up for a mean of 24 months (range: 14-34) only two patients required admission for a new episode of UC and colectomy was finally indicated in only one. None of the 14 patients treated with cyclosporine showed severe adverse effects attributable to the drug. CONCLUSIONS Intravenous cyclosporine is a safe and effective alternative in the treatment of severe episodes of steroid-refractory UC. Early initiation of oral administration associated with azathioprine is useful in maintaining response, reducing subsequent relapses and the need for colectomy during the follow-up of these patients.