: Both pathogenic and normal enteric microflora can induce and perpetuate chronic intestinal inflammation with systemic manifestations in genetically susceptible hosts. At the present time, there is no convincing indication that the majority of cases of ulcerative colitis or Crohn's disease is caused by persistent infection by Mycobacterium paratuberculosis, measles, Listeria monocytogenes, or Helicobacter species, but this possibility remains a valid hypothesis. Transient infection with any of a number of pathogens including upper respiratory tract infections and common enteric pathogens could provide one of the environmental triggers that initiate or reactivate IBD, which is then perpetuated in susceptible hosts by resident (not pathogenic) commensal luminal bacteria. Recent results in animal models demonstrate the absence of colitis, gastritis, and arthritis in a sterile (germ-free) environment, showing the importance of resident bacteria as persistent antigenic stimuli in the genetically susceptible hosts. Furthermore, there is an indication that not all normal luminal bacteria have equal capacities to induce mucosal injury, since some species can induce inflammation (Bacteroides), some are neutral (E. coli) and others may be protective (Lactobacilli). These observations have important therapeutic implications, such that altering luminal bacterial components and thereby decreasing the persistent antigenic drive offer alternative or adjuvant approaches to ongoing efforts to block mucosal immune responses to these stimuli.