Once regarded as medical curiosities, ulcerative colitis and Crohn's disease have achieved a remarkable change in status recently and today are among the more compelling of all human illnesses. The cause(s) of inflammatory bowel disease (1131)) are not known. Genetic, environmental, microbial, and immunologic factors are involved, but the precise mechanisms are obscure. The incidence of ulcerative colitis is relatively stable, while Crohn's disease continues to increase in frequency. In 10% to 15% of patients, it is hard to differentiate between ulcerative colitis and Crohn's colitis; however, problems with diagnosis usually resolve with time and repeated examinations. In part I of his two-part monograph on IBD, Dr. Kirsner addresses the nature and pathogenesis of the disease. Increased study of ulcerative colitis and Crohn's disease in recent years has generated new knowledge regarding their etiology. Part I focuses on microbial, immunologic, and genetic mechanisms and the inflammatory processes involved in the disease. In part 11, which will be presented in next month's issue of Disease-a-Month, Dr. Kirsner deals with the clinical features, course, and management of IBD, based on the author's 55 years of experience with these problems and supplemented by critical examination of the recent (1988–1990) literature. Particular attention is directed to the symptoms and physical findings of ulcerative colitis and Crohn's disease, the laboratory, radiologic, endoscopic, and pathologic features, and the many systemic complications. The IBDs are mimicked by several enterocolonic infections and other conditions, making differential diagnosis necessary. Inflammatory bowel disease in children and the elderly conforms to conventional clinical patterns modified by the health circumstances of the respective age groups. Because the cause of IBD has not been established, current medical therapy is facilitative and supportive rather than curative. The principles of medical treatment are approximately the same for ulcerative colitis and Crohn's disease. Treatment emphasizes a program rather than a drug and also considers the individuality of the therapeutic response. A clearer understanding of dietary and nutritional needs, including hyperalimentation and electrolyte and fluid balance, aids treatment. Antidiarrheal and antispasmodic preparations and sedatives are prescribed for symptom relief. The bowel inflammation is controlled with sulfasalazine or the newer 5-amino salicylic acid (5-ASA) compounds, antibacterial drugs for complications of Crohn's disease and IBD, adrenocortical steroids, and the immunosuppressive compounds 6-mercaptopurine (6-MP), azathioprine, and cyclosporine, as determined in each patient. The surgical procedures available for treatment of ulcerative colitis include total proctocolectomy and ileostomy or ileoanal anastomosis. In Crohn's disease of the small bowel, the usual approach is intestinal resection and re-anastomosis. Strictureplasty is possible in some instances of stenotic intestinal disease. For treatment of Crohn's colitis, procedures include total proctocolectomy and ileostomy, subtotal colectomy and ileorectal anastomosis, and very occasionally, segmental resection of the large intestine. p ]Chronic IBD requires prolonged observation, periodic adjustments in therapy, and colonic and radiologic surveillance. The prognosis of ulcerative colitis and Crohn's disease is much improved over the years, but a cure has not yet been found, reemphasizing the need for further investigation of these challenging diseases.