BACKGROUND & AIMS: The follicle-associated epithelium (FAE) over mucosa-associated lymphoid tissues consists of distinct enterocytes and M cells concentrated at its periphery. The basement membrane composition was analyzed to test whether differences account for the distinct differentiation programs along the crypt-villus and crypt-FAE axes. To determine whether the decreased number of M cells in the FAE apex is caused by premature extrusion, we mapped the site where they undergo apoptosis. METHODS: The FAE basal lamina of Peyer's patches from BALB/c mice was analyzed by immunochemistry. M cells were identified using the Ulex europaeus agglutinin lectin. The cell proliferation and apoptotic compartments were characterized using bromodeoxyuridine incorporation and the TUNEL assay. RESULTS: The perlecan and laminin 2 stainings were different in FAE and villi. Myofibroblasts were absent beneath the FAE. The migration kinetics of cells along the FAE was similar to that along the villi. Apoptotic cells were detected exclusively at the apex of the FAE. CONCLUSIONS: FAE and M-cell differentiation is associated with a distinct basal lamina composition. FAE enterocytes express transient M-cell features as they move from the crypts toward the apoptotic compartment. M cells have a highly plastic phenotype that raises interesting questions about the control of intestinal epithelial cell differentiation.