Ontogeny of reticulum cells (RC) in the rat intestine in relation to the development of the gut-associated lymphoid tissue (GALT) was studied using a panel of monoclonal antibodies (mab) directed against RC in peripheral lymphoid organs, ED10-ED15. The mab ED10 specific for RC in the spleen T cell area, recognized an epitope on gut RC, which cells seem to be involved in the influx and accumulation of lymphocytes in the lamina propria and in Peyer's patches (PP) and proximal colonic lymphoid tissue (PCLT). The mab ED11 which recognizes RC in the T cell area and B cell follicles of spleen, stained follicular dendritic cells (FEC) in the B cell area of the mesenteric lymph node (MLN), PP and PCLT. The ED11 expression occurs earlier and reveals stronger staining in MLN as compared to those in PP and PCLT, suggesting the prominent role of MLN in the generation and proliferation of B cells in the gut mucosal immune system. The mab ED13 specific for RC in the B cell area of the lymph nodes, stained the basement membrane of the epithelium overlying PP and PCLT, and high endothelial venules (HEV), suggesting that this might be involved in providing the microenvironment for the development and differentiation of follicle-associated epithelium, and facilitating lymphocyte traffic. The mab ED12 specific for RC in the paracortex of peripheral lymph nodes, gave a diffuse nonspecific staining in the gut, whereas mab ED14 and ED15 are markers for common connective tissue cells. We conclude that the gut RC are morphologically and phenotypically heterogenous. ED10+, ED11+, and ED13+ RC are probably involved in the development of the gut lymphoid microenvironment.