The intestinal mucosa is the largest surface area in the body which is continually exposed to an enormous amount of food antigens, viruses, bacteria, parasites or the by-products of these organisms. In such an antigen-loaded environment, specialized defence mechanisms must exist. There is clear evidence that the function of lymphocytes in the intestinal mucosa (IELs or LPLs) is different from that of lymphocytes of the peripheral blood, lymph node or spleen (these are antigen-free organs). The basic processes of these reactions are not completely understood. The role of differential antigen handling and presentation, and the non-random distribution of responsibilities between the professional and non-professional APC in this regard, have not been characterized. Thus, much remains to be learned about the basic mechanisms of antigen uptake, processing and presentation in the intestine which are necessary to induce an immune response. Diversity in APC function is a natural requirement for the maintenance of homeostasis in the intestine. Subpopulations of professional and non-professional APC may have been programmed to function in such a way that non-professional APCs may play a dominant role. It is anticipated that in vivo model systems will be developed and that eventually a clearer understanding will be gained in this rapidly evolving field.