A study was conducted to evaluate the influence of natural exogenous antigen stimulation on the development of lymph follicles in the peripheral lymphoid organs of the rat. The number of lymph follicles and germinal centers per popliteal node as well as the morphological features of popliteal nodes, mesenteric nodes and Peyer's patches were compared between 8-week-old male Sprague-Dawley rats reared in germ-free, specific pathogen-free (SPF) and conventional environments. In mesenteric nodes and Peyer's patches from conventional and SPF rats, almost every follicle contained a germinal center. In the mesenteric nodes from germ-free rats, only 9 of 195 lymph follicles examined contained a germinal center, but interestingly, in Peyer's patches all the lymph follicles examined showed a fairly well developed germinal center. The popliteal nodes from germ-free rats had no germinal centers and each node contained about 80 lymph follicles. In six conventional rats and two of five SPF rats used, the number of lymph follicles per popliteal node usually ranged from 100 to 130, and some lymph follicles contained a germinal center. However, in the other three SPF rats the popliteal node on both sides showed no germinal center, and each contained almost the same number of lymph follicles as the popliteal nodes of other SPF and conventional rats. The present results are consistent with the view that even in the absence of exogenous antigen stimulation, a regional lymph node of the germ-free rat develops a substantial number of primary lymph follicles by way of a non-immunological cellular activity, and that natural exogenous antigens may influence the development of lymph follicles by stimulating the cellular activity rather than evoking the humoral immune responses.