Human fractalkine and its apparent murine counterpart neurotactin are the only members identified so far of the CX3C subfamily of chemokines, Recently, a human fractalkine receptor was identified and named CX(3)CR1, Here we have identified a mouse counterpart of this receptor. The receptor was identified by analysis of a mouse genomic clone named PC2 isolated by homology hybridization using CX(3)CR1 as probe. Clone PC2 has a 354-codon open reading frame that has 83% amino acid identity to CX(3)CR1. PC2 RNA was abundant in brain and lung and comparatively less abundant in lung, liver, kidney, testis, and peripheral blood leukocytes, a pattern similar to that found for CX(3)CR1. The recombinant fractalkine, but no other chemokines tested, induced chemotaxis and transient increases in [Ca2+](i) in HEK 293 cells transfected with PC2, whereas untransfected cells did not respond. Furthermore, fractalkine bound specifically to the transfected cells (K-d = 4 nM). Thus, fractalkine is a functional ligand for this receptor and we propose to name it mCX(3)CR1 for murine CX3C chemokine receptor 1. (C) 1998 Academic Press.