A human cDNA encoding a putative G protein-coupled receptor designated chemokine beta receptor-like 1 (CMKBRL1) was isolated from an eosinophilic leukemia library. Its deduced sequence is approximately 40% identical to previously cloned receptors for the beta chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha), RANTES, and monocyte chemoattractant protein-1 (MCP-1), which are chemoattractants for blood leukocytes, and is 83% identical to the product of the orphan rat cDNA RBS 11. Like the MIP-1 alpha/RANTES receptor, CMK-BRL1 is encoded by a small, single-copy gene that maps to chromosome 3p21 and is expressed in leukocytes. However, two screening assays with a broad panel of chemokines failed to identify its ligand. CMKBRL1 mRNA was detectable by Northern blot hybridization in neutrophils and monocytes, but not eosinophils, and was also found in eight solid organs that were tested with particularly high expression in brain. The RNA distribution of the known beta chemokine receptors was overlapping but distinct from that of CMKBRL1. MIP-1 alpha/RANTES receptor mRNA was detectable in neutrophils, monocytes, eosinophils, and in all eight solid organs tested, with particularly high expression in placenta, lung, and liver. MCP-1 receptor mRNA was found in monocytes, lung, liver, and pancreas. These results suggest that the ligand for the putative CMKBRL1 receptor is a beta chemokine that targets both neutrophils and monocytes. Moreover, the RNA distributions suggest that CMKBRL1, the MIP-1 alpha/RANTES receptor, and the MCP-1 receptor may have both overlapping and distinct biological roles.