The C-C chemokines human monocyte chemoattractant protein-1 and -3 (MCP-1 and MCP-3) and mouse JE and FIC are potent activators of monocytes. Several receptors for MCP-1 and MCP-3 have been cloned from human monocytic cell lines, and one of these receptors, CCR2B, binds both MCP-l and MCP-3. Thus far, no murine receptors for JE or FIC have been reported. We have cloned a novel murine C-C chemokine receptor, designated mouse CCR2 (mCCR2), from the mouse monocyte cell line WEHI265.1. The predicted 373-amino acid sequence of mCCR2 shows highest identity (80%) with CCR2B. When stably expressed in human embryonic kidney 293 cells, mCCR2 specifically bound 125I-JE with high affinity. FIC was less potent than JE in competing 125I-JE binding to mCCR2-expressing cells, while three other mouse chemokines, MIP-1alpha, C10, and N51/KC, did not compete. mccr2 mRNA expression was detected in elicited peritoneal macrophages as well as in several mouse organs. The cloning of mCCR2 provides an important tool to investigate monocyte/macrophage responses to JE and FIC, to identify other targets for their action, and potentially to study models of CCR2 function in the mouse.