Peyer's patch lymphoid follicles are characterized by a cuboidal epithelium, which has low numbers of mucus-secreting goblet cells, infiltration with clusters of lymphoid cells, and unique antigen-transporting M cells. M cells have short, irregular microvilli similar to undifferentiated crypt epithelial cells, which suggested that M-cell renewal might occur over follicle surfaces. By autoradiography we found that epithelial renewal over follicles only occurs by proliferation in multiple adjacent crypts with cell migration onto follicle surfaces. Nuclear labeling of M cells was observed after 72 h among fully differentiated cuboidal cells from which M cells appear to develop. Goblet-cell flow from surrounding crypts supplied large numbers of goblet cells to adjacent villi, but it was remarkably restricted onto the Peyer's patch follicle surfaces, creating a breach in the mucus barrier that may facilitate antigen sampling.