In recent years it has been possible to establish animal models with colitis by immunological and genetic manipulation. Such animal models share characteristic features with human inflammatory bowel disease. The fact that different immune defects induce inflammation in the intestines supports the theory of heterogeneity in the pathogenesis of human inflammatory bowel disease. Discrepant results concerning the disease association with genetic markers have been obtained in different populations, which may confirm the concept of heterogeneity. So far it has not been possible to identify one single factor which is aetiologically responsible for the development of inflammatory bowel disease. The intestinal inflammation is normally T cell-dependent and caused by a dysbalance of pro- and anti-inflammatory immune responses. Interestingly, animals kept under germfree conditions do not develop disease. Thus, the intestinal bacterial flora plays a crucial role. The loss of immune tolerance towards these bacterial antigens is an important current concept in the pathogenesis of inflammatory bowel disease.