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Severely ill patients with ulcerative colitis are usually treated with parenteral corticoids. Those with signs of systemic toxicity usually receive antibiotics as well. However, the role of antibiotics in patients without high fever, profound leukocytosis, peritoneal signs or mega-colon is not clear. Since 1985, seven patients who were admitted to the hospital with severe ulcerative colitis but without signs of toxicity have received broad spectrum antibiotics. The patients ranged in age from 21 to 65 years: four were male; all were white. Stools for infectious agents were negative. Each patient received intravenous prednisolone at a dose of 60 mg/24 h. After 7 days, each patient continued to have eight to 10 bloody stools per day with low-grade fever and leukocytosis. Institution of broad-spectrum antibiotics was associated with a striking resolution of bloody diarrhea and normalization of temperature. No patient has required co-lectomy in follow-up of 2–9 years. Whether the antibiotics are treating an undetected pathogen or eliminating non-pathogenic bacteria contributing to the inflammatory process is not clear. I suggest that severely ill patients with ulcerative colitis deserve a trial of antibiotics before being considered failures of medical therapy.