Tumor necrosis factor-alpha (TNF alpha)-neutralization by infliximab has previously proven efficacious in chronic active Crohn's disease (CD). We performed an open-label pilot study of a single infusion of 5 mg/kg infliximab in six patients with severe active, steroid-refractory ulcerative colitis (UC). Clinical activity was evaluated according to Lichtiger on days -1, day 7, and day 28. Colonoscopy with biopsy was performed on day -1 and day 7. All patients showed marked clinical improvement by day 7 (Lichtiger score 16.3 +/- 0.4 [day -1] vs 4.8 +/- 0.7 [day 7], p < 0.0001). Four of six patients had long-term remission (Lichtiger score 7.7 +/- 2.2 [day 28], P < 0.01 compared to day -1), with a median follow-up of 5.5 months. Colonoscopy confirmed significant healing of endoscopic lesions. The inflammatory infiltrate disappeared on H&E stains, with a marked reduction in infiltrating neutrophils. Semiquantitative evaluation of T and B lymphocytes and macrophages by immunohistochemistry did not reveal major differences compared to pre-treatment. Apoptotic cells in the mucosa were reduced on day 7. Our data point toward a novel efficacious treatment option in severe steroid-refractory UC and raise the need for controlled trials.