We wished to determine the effect of appendectomy and tonsillectomy on the subsequent risk for development of ulcerative colitis (UC). We conducted a case-control study at the University of Oklahoma Hospital and VA Medical Center gastroenterology clinics, as well as at the offices of private physicians. Subjects being followed for UC formed the study group. Patients being followed at Internal Medicine Associates of the University of Oklahoma clinics formed the controls. We recorded the patient's name, age, sex, race, history of smoking, and history of appendectomy or tonsillectomy. The study group consisted of 193 patients, and there were 394 controls. The prevalence of appendectomy was lower (17.8% vs 5.2%) among patients with UC (P < 0.01). The prevalence of tonsillectomy was similar in the two groups (20.6% vs 18.1%; P = NS). We conclude that appendectomy is associated with a decreased risk for subsequent development of ulcerative colitis.