We have used cyclosporin to treat patients with acute steroid-resistant ulcerative colitis since the beginning of 1991. Of the 55 patients so far elected for treatment, 40 received the drug intravenously at 2 mg/kg/day for 14 days, with the responders being maintained on traditional soft-gelatin-capsule cyclosporin at a dose of 6-8 mg/kg/day for 6 months; the remaining 15 received oral microemulsion cyclosporin, 5 mg/kg/day, for 3 months. The doses were titrated to ensure whole-blood drug concentrations of 60-240 ng/ml, with levels of approximately 200 ng/ml being attained by both regimens. One-hundred percent of the patients receiving oral microemulsion cyclosporin and 65% of those receiving the intravenous regimen achieved a short-term response (p = 0.011). Both the responder subsets received additional azathioprine and relapsed on treatment with the same frequency of 40%. However, 17% of the patients who received intravenous cyclosporin developed major toxicity (including one fatality), whereas no major toxicity was observed in the oral microemulsion cyclosporin group. The microemulsion formulation was therefore more effective than intravenous cyclosporin in achieving the short-term remission of steroid-unresponsive ulcerative colitis. As the maintenance drug, it led to the same frequency of disease relapse as traditional oral cyclosporin. However, because it did not involve invasive in-hospital procedures or cause major toxicity, it was more efficient than the combination of the intravenous and traditional oral drug.