The relative adherence of follicle associated and nonfollicle associated epithelial cells in intestinal lymphoid tissues was compared morphologically. Incubation of Peyer's patches and appendix with hyaluronidase resulted in detachment of M cells and other epithelial cells overlying lymphoid follicle surfaces but not of villus or colonic epithelial cells. Enzymatic treatment of intestinal lymphoid tissues produced superficial erosions of follicle epithelium which exposed a porous and fenestrated basal lamina. After enzymatic treatment, detached M cell-containing follicle epithelium was characterized by intracellular vacuoles, widening of intercellular spaces, cell rounding, disappearance of microvilli, and loss of M cell-lymphocyte associations. Enzymatic treatment was responsible for removal of follicle epithelium, since Peyer's patches and appendix tissues incubated with medium alone did not exhibit appreciable epithelial detachment. These results, showing that the adherence of epithelial cells overlying intestinal lymphoid follicles is more labile than that of villus and colonic epithelial cells, may be of pathophysiologic significance in follicle ulcerative processes.