The stimulus for the immune response in Crohn's disease is unknown. In each of 19 cases of Crohn's disease evaluated by electron microscopy, epithelial cells of the ileum contained phagolysosomes with lamellar layers of lipid. These structures, now termed R or reactant bodies, are the proffered antigenic stimulus. They are proposed to be an amalgam of lipid (cholesterol esters, or phospholipids) and bacterial fragments (mycoplasma, mycobacteria or streptococci), which in combination are hypothesized to produce a powerful immunological response analogous to the adjuvant effect. For disease expression to occur, lipids and specific bacterial populations are needed in the bowel lumen. These factors may account for the success of elemental diets that are low in fat in the treatment of Crohn's disease and for the regional distribution of disease along the intestinal tract.