We have defined two receptors involved in the binding of erythroblasts and other developing hematopoietic cells to murine macrophages. With 14-day-old fetal liver macrophages, which exclusively interact with erythroid cells in vivo, a divalent cation-dependent adhesion receptor, EbR, is able to mediate reversible attachment of erythroblasts in vitro. With adult resident bone marrow macrophages, which naturally bind a mixture of myeloid and erythroid cells, two distinct receptors are involved. Most of the binding is mediated by an EbR-like divalent cation-dependent receptor. The remainder is mediated by a divalent cation-independent receptor, SER, which was originally discovered by its ability to bind unopsonized sheep erythrocytes. To date, the molecular nature of EbR is unknown, but the failure of certain antisera and specific inhibitors to block its activity indicates that EbR may be a novel macrophage adhesion receptor. SER has recently been characterized by means of a monoclonal antibody selected on the basis of its ability to block binding of sheep erythrocytes. SER is a 185-K plasma membrane glycoprotein expressed specifically by resident bone marrow macrophages. Inhibition experiments have demonstrated that SER is able to mediate binding of erythroid and myeloid cells via recognition of sialylated glycoconjugates. The possible functions of EbR and SER in macrophage-hematopoietic cell interactions are discussed.