Accumulating evidence indicates that the inflammatory bowel diseases result from an activation of immune and inflammatory responses initiated by a stimulation of the luminal flora or their products. Genetically determined variations in key mucosal functions, including cell activation by prototypic bacterial pattern molecules, lead to differential susceptibility to the development of these disorders, probably reflecting an interrelated activation of the innate and adaptive immune responses. The persistence and amplification of inflammation is likely to reflect the continuing presence of the driving stimulus and the complex, self-reinforcing activation of select T-helper subtypes and macrophages and other antigen-presenting cells, mediated by several cytokines. The latter include interleukins-2, 12, and 18 as well as interferon and macrophage migration inhibitory factors. The production of other broadly pro-inflammatory cytokines, most notably tumour necrosis factor and interleukins-1 and 6, enhances related inflammatory processes that eventually lead to many of the clinical manifestations of inflammatory bowel disease. The overall severity of the inflammatory process reflects a balance between leukocyte recruitment and downregulatory mucosal repair processes.