Ulcerative colitis and regional enteritis (Crohn's disease), probably first appeared as isolated cases, several centuries ago; but not until the latter half of the 19th century did their clinical presentation attract medical interest as definable entities. This review of the early medical literature reveals a surprising number of reports of inflammatory bowel disease consistent with present descriptions of these conditions. As with other diseases, the steadily increasing numbers of patients with ulcerative colitis during the first third of the 20th century and of patients with regional enteritis during the latter two thirds of the century follows a familiar pattern encountered with diseases wherein environmental factors play a pathogenetic role. The early history of ulcerative colitis is lost in the complex mixture of infectious colitides, only partially unraveled in the past 100 years. The early history of regional enteritis probably is linked with the numerous European and American reports of tumor-like granulomas of the small intestine, initially regarded as neoplastic lesions requiring surgical removal. It now seems possible that physicians over a period of several centuries may have encountered these conditions but were not in a position to appreciate their uniqueness. The careful accounts of many authors, especially Morgagni (1761), Wilks (1859), Fenwick (1889), Dalziel (1913) and of Crohn, Ginzburg, and Oppenheimer (1932) of then obscure intestinal inflammatory processes thus re-emphasizes the importance of meticulous clinical and pathological descriptions in the subsequent elucidation of obscure disorders. If the course of ulcerative colitis and of Crohn's disease follow the historical pattern of other once important and later disappearing human illnesses, we may have reason to anticipate clarification of their etiology and possible relationship in the not too distant future.