Peyer's patches in the intestinal mucosa are characterized by the presence of several lymphatic follicles and interfollicular T-cell regions. Luminal antigens are transported across the intestinal epithelium to stimulate the Peyer's patch pre-B-cells in the follicles that proliferate and migrate to distant sites. Evidence suggests that antigen priming of B-lymphocytes is responsible for the number and location of Peyer's patches during postnatal life, but little is known about the histogenesis of Peyer's patches and their overlying membranous (M) cells. To examine whether T- and B-lymphocytes in Peyer's patches have an influence on M-cell generation, we studied the development of Peyer's patches and M-cells in severe combined immunodeficient (SCID) mice reconstituted with bone marrow cells from normal syngeneic mice. Our experiments demonstrate that the donor bone marrow cells in the host scid mice repopulate to form single (primary) follicles and aggregates of lymphoid nodules, the Peyer's patches. Use of the lectins Anguilla anguilla (AAA) and Ulex europaeus I (UEA-I) as positive markers of mouse Peyer's patch M-cells revealed that M-cells develop in the dome epithelium overlying the single primary follicles and Peyer's patches of reconstituted scid mice. This experimental system therefore allows the study of the histogenesis of Peyer's patches and M-cells.