We studied the clinical effects of long-term immunosuppressive treatment in 42 patients with severe Crohn's disease and extensive colonic involvement. Mean observation period before and after start of therapy exceeded 5 years. All but one of the patients receiving azathioprine or 6-mercaptopurine improved, and 11 of 42 attained complete remission during therapy. Cyclophosphamide was substituted for azathioprine with inferior results in four patients with pancreatitis soon after initiation of azathioprine therapy. The frequency of both local and systemic complications decreased significantly during the period of therapy. Prednisolone could be withdrawn in 25 patients and reduced to less than 7.5 mg every other day in the others. The average remission period after withdrawal of all drugs in 10 patients was 40 months. The results were superior to those in a surgical series with comparable observation time drawn from the same background population. Aside from pancreatitis in four patients, no serious side effects were seen. Fertility was unaffected. The data demonstrate the feasibility of long-term azathioprine (6-mercaptopurine) treatment in extensive Crohn's disease.