The inflammatory bowel diseases, Crohn disease and ulcerative colitis, are complex disorders whose etiology and pathogenesis have eluded precise definition despite decades of research. They clearly have multiple interactive components, especially genetic, environmental, and immunological factors. The leading hypothesis has been that the chronic intestinal inflammation is due to a dysregulated mucosal immune response to enteric bacterial antigens in a genetically susceptible host. In recent years evidence has emerged from novel experimental models of chronic intestinal inflammation that strongly supports this hypothesis. Many of these newer models are the result of the recently developed ability to manipulate the genome of mice either selectively deleting (knockout) or inserting (transgenic) genes of interest. These “ induced mutants “ are revealing the critical molecules and cells that maintain normal intestinal homeostasis in the face of massive antigenic challenge. T cells have been found to be the major effector cells sustaining chronic intestinal inflammation. Other subsets of T cells are regulatory cells that can prevent intestinal inflammation. In most models where it has been examined, the bacterial flora induces and localizes the disease. Lastly, multiple genes have been shown to contribute to disease susceptibility. Parallel advances in each area are being made in studies of patients. Together, these approaches have great promise for a more profound understanding of these disorders which in turn should lead to new and better treatments. © 2000, The Japanese Society of Gastroenterology. All rights reserved.