Perforation of the colon occurred in thirteen patients receiving corticosteroids for diseases unrelated to the bowel. Treatment averaged 3.5 years. The paucity of symptoms, signs, and laboratory indexes of visceral perforation led to frequent delays in treatment and to incorrect preoperative diagnoses in all but three patients. The perforations were often unusual in location (cecum, hepatic flexure, and multiple points in the transverse and descending colon) and often resulted from single punched-out ulcers in otherwise normal bowel. In seven patients the lesion could not be distinguished from perforated sigmoid diverticulitis, but in two of these patients the ulcerations were found in adjacent diverticula. The evidence strongly suggests that corticosteroids can be responsible for ulceration and perforation of the colon either by direct injury or by interference with normal mechanisms of bowel repair.