A 28-year-old man with chronic ulcerative colitis had a proctocolectomy with creation of a continent ileostomy. Six months later, he developed a severe systemic illness characterized by malaise, 24-lb. weight loss, fever, night sweats, arthralgias, bloody diarrhea, and problems with ileostomy function. On endoscopy, the pouch showed erythema, edema, friability, and ulceration; on biopsy, there was severe mucosal disruption with ulceration into the submucosa. Features consistent with chronic ulcerative colitis were also present. Laboratory investigation ruled out other causes of the illness so that a diagnosis of pouch ileitis was made. The patient responded dramatically to a 10-day course of metronidazole and remains well 2 years later. In patients with continent ileostomy after proctocolectomy for chronic ulcerative colitis, inflammation of the pouch may be associated with a severe systemic illness. The pathogenesis is unclear, but may involve the interaction of colonic type bacterial flora with ileal mucosa in immunologically susceptible patients.