The ontogeny of reticular cells in the ileal Peyer's patch of sheep from 70 days gestational age was studied by light and electron microscopy and by enzyme histochemistry. Small to medium-sized lymphocytes were seen in the lamina propria at 97 days, when the stroma was essentially still mesenchymal. By 110 days, the stromal cells in the dome/follicle primordia had differentiated into reticular fibroblasts, whose processes and fibers were seen to surround groups of lymphocytes. With advancing age the number and size of primordia increased, and proliferation was obvious among the lymphocytes. Processes of reticular cells increased in number and penetrated between individual lymphocytes of the groups. Coarser desmosome-like contacts were seen between the reticular cells from 115 days onwards. A central light area in the follicle was apparent from 130 days onwards. The fine structure of the stromal cells in this light follicle center developed towards but never became similar to that of follicular dendritic cells in a typical germinal center. The fine interdigitating end branches of the stromal cells were less numerous, and the dense homogeneous material present in between the end branches was not observed in the ileal Peyer's patch follicle. Instead, small particles and vesicles were seen between the various cell types of the light center and were not restricted to the intercellular spaces between the stromal cells. In the dark peripheral zone of the follicle, the stromal cells retained more immature features. The follicle became bordered by a capsule at an early stage. This capsule was formed by multiple layers of flattened fibroblasts separated by small amounts of intercellular material only. The alkaline phosphatase, Mg(2+)-dependent adenosine triphosphatase and 5' nucleotidase reactivities of the follicular dendritic cells in the ileal Peyer's patch were similar to those of early prenatal primary follicles of sheep lymph nodes. This study indicates that the stromal cells of the ileal Peyer's patch are mesenchymal in nature and different from those of germinal centers and the epithelial stromal cells of bursa Fabricii of birds.