A C1q receptor that upregulates the phagocytic capacity of professional phagocytes, C1qRp, has been identified, and its primary structure determined by cDNA cloning and sequencing. Monoclonal antibodies that immunoprecipitate this 126,000 Mr polypeptide inhibit the enhancement of phagocytosis triggered not only by C1q but also by mannose binding lectin (MBL) and pulmonary surfactant protein A (SPA) providing critical evidence that this polypeptide is a functional receptor or component of the receptor that mediates this enhancement of phagocytosis. The amino acid sequence, deduced from the cloned cDNA coding for this receptor, indicates that this surface glycoprotein receptor is a novel type I membrane protein of 631 amino acid containing a region homologous to C-type lectin carbohydrate recognition domains, 5 EGF-like domains, a single transmembrane domain and a 47 amino acid intracellular domain. Expression of this receptor is limited to cells of myeloid origin, platelets and endothelial cells, consistent with a relatively selective function, and making it an attractive candidate for therapeutic modulation of function. A distinct C1q receptor that triggers superoxide in polymorphonuclear leukocytes has been functionally characterized and designated as C1qRO2-. Thus, the accumulated data that will be summarized here demonstrate that there are at least two C1q receptor/receptor complexes (C1qRp and C1qRO2-), each triggering distinct cellular responses, that multiple C1q receptors can be expressed on the same, as well as on different, cell types, and that at least one C1q receptor, C1qRp, is capable of responding to multiple ligands.