The immunoregulatory proteins CC chemokines are potent chemoattmctants of lymphocytes and monocytas, as wail as acttvators and attmctants of eosinophlk and basophlls. We have itrotated a cDf4A that encodes a seven transmembmne-spanning receptor, wlth homology to other chemorttrcrctwrt receptors, that encodes a proteln designated CC CKR-1 that acts as a mceptor for the CC chemokines. Human and murlne macrophege lnffemmatory protein la (MIP-la), human macrophage lnflammatory protein 10 (MIP-l (i), human monocyte chemotactlc protein 1 (MCP-l), and RANTES all bind to the CC CKR-1 wlth varying afftnities. Chemoklne Mnding affintty does not predict how wdl the llgsed wHI transmit a signal through the recap tor: RANTES and human &HP-la Induce a similar intracellular calcium flux white blnding wlth dteparate affinities, whlk MCP-1 and human MIP-lg Induce calcium mobiltzatlon only at high concentrations. Finally, CC chemokines were shown to bind a CC CKR-1-related gene product encoded by cytomegatovirus, suggesting a role for CC chemokfnes in viral immunity.