Experiments were carried out to elucidate the cellular origin of the dendritic reticulum cell (DRC). The monoblastic cell line THP-1, the histiocytic cell line U-937, and the mononuclear cell fraction from peripheral blood (PMC) were stimulated with supernatants from lectin-stimulated peripheral blood lymphocytes and from stimulated T- and B-cell lines. Differentiation towards DRC was assessed by immunocytochemical demonstration of the DRC-specific antigen Ki-M4. Supernatants from isolated peripheral T lymphocytes and from T- and B-cell lines were capable of stimulating THP-1 to Ki-M4 antigen expression, whereas U-937 and the PMC fraction remained negative for this antigen throughout the experiments. These results provide further evidence for a relationship of DRCs with the mononuclear-phagocytic cell system and hence for their bone marrow origin. Furthermore, the data suggest that soluble factors of T and/or B cells are involved in mediating the differentiation process of precursor cells to DRC.