We have cloned the murine homologue of human CC Chemokine Receptor-4 (CC CKR-4). In equilibrium competition binding assays performed in undifferentiated HL-60 cells transfected with human and murine CC CKR-4 cDNA, the IC50 values for the binding of [125I]macrophage inflammatory protein-1 alpha to human and murine CC CKR-4 were 14.5 +/- 9.0 nM and 10.1 +/- 3.0 nM, respectively, and the IC50 values for the binding of [125I]RANTES to human and murine CC CKR-4 were 9.3 +/- 3.0 nM and 5.7 +/- 2.6 nM, respectively. The cDNA clone for murine CC CKR-4 is 1531 bp, and the largest open reading frame encodes a protein of 360 amino acids that is 85% identical to human CC CKR-4. Murine CC CKR-4 was detected in the thymus and T-cell lines by Northern blot analysis. This first report of direct binding of chemokines to CC CKR-4 demonstrates that the highly homologous human and murine receptors have similar binding characteristics and tissue distribution.