The clinical course and prognosis of ulcerative colitis was studied in a group of 413 Greek patients. The study lasted for 16 years and follow-up was achieved in 95% of the patients. Both sexes were almost equally affected, mainly between the ages of 40-49. Most of the patients lived in cities and had high educational levels. Familial clustering for inflammatory bowel disease was found in 2.7% of the patients. In most of them the disease was confined to the rectosigmoid area or left bowel and was of mild to moderate severity. The disease course included exacerbations-mainly of mild to moderate severity-and remissions. Mortality was absent during first attack, and it was generally low at the completion of the study. Excluding deaths caused by colorectal cancer, most of the deaths were unrelated to the ulcerative colitis itself. Unusual combinations of ulcerative colitis with other diseases, including diseases of autoimmune origin, were noted. There were no differences between men and women in the various clinicoepidemiologic parameters or in the course of the disease. Surgery was performed in 16.7% of patients, whereas surgery at first attack was required in 0.5%. In comparison with the nonoperated group, patients who were operated on were significantly younger at the time of onset of symptoms and had significantly more extensive disease. Factors prognostic of severe attacks and colectomy were extensive disease, young age at onset, and severe recurrences. Evolution to cancer was observed in 1.45%, whereas extraintestinal cancers also appeared in 1.5%. At the completion of the follow-up period, 5.8% of the patients were dead, 16% had only one attack, 2.7% experienced continuous symptoms, whereas in 58.8% of them, the disease course included exacerbations and remissions. On the basis of the outcome of severe attacks and the more favorable short-term prognosis, it could be argued that ulcerative colitis in Greece runs a milder course compared with that of other developed countries in Western Europe and North America.