We studied the natural history of ulcerative colitis (UC) by following 1116 patients in whom UC had been diagnosed or confirmed at The Cleveland Clinic Foundation between 1960 and 1983. Data before 1973 were obtained retrospectively. Criteria for inclusion in the study were: a diagnosis of UC confirmed by clinical, radiographic, endoscopic, and histologic examination; disease location that could be defined as one of three categories (proctosigmoiditis, pancolitis, or left-sided colitis); and a follow-up of at least five years (mean=12.7 years). Mean age at diagnosis was 32 years. Of the 1116 patients, 46.2% (516) had proctosigmoiditis; 36.7% (410) had pancolitis (colitis of the entire large intestine); and 17.0% (190) had left-sided colitis (from the dentate line to the splenic flexure). Early complications (within two years of diagnosis) included colonic hemorrhage (16.7%) and toxic colitis (12.7%). Complications were highest among patients with pancolitis. Surgery was required for 37.6% of the patients. Primary indications for surgery included chronic or intractable disability (40.2%), fulminating medical failure (16.9%), and colonic dilatation (18.4%). At the most recent follow-up, the disease had extended (progressed to a more serious category) in 53.8% of the patients, although 67.2% were asymptomatic and only 37.0% were on medications. Both the final disease destination and the initial diagnosis impacted cumulative colectomy-ileostomy rates. Factors associated with extension were toxic colitis (P<0.0001); extent of disease at diagnosis (P<0.0001); joint symptoms (P=0.0008); younger age at diagnosis (P=0.06); and severe bleeding (P=0.07).