CX3CR1 is a GPCR expressed on natural killer cells, cytotoxic T lymphocytes, and macrophages. The sole ligand for CX3CR1, fractalkine, is an unusual chemokine that is expressed as a transmembrane molecule with a CX3C domain and a mucin domain (Imai et al., 1997). Fractalkine is highly expressed on endothelial cells activated by TNFα and other proinflammatory cytokines, and fractalkine/CX3CR1 interactions mediate recruitment of macrophages into the atherosclerotic plaque (Lesnick et al., 2003; McDermott et al., 2003). In addition, fractalkine and CX3CR1 have been implicated in the pathogenesis of glomerulonephritis, HIV infection and rheumatoid arthritis (Ito et al., 2002; Faure et al., 2003; Nanki et al., 2002). Chemicon's cloned human CX3CR1 -expressing cell line is made in the Chem-4 host, which supports high levels of recombinant CX3CR1 expression on the cell surface and contains high levels of promiscuous G proteins to couple the receptor to the calcium signaling pathway. Thus, the cell line is an ideal tool for screening for antagonists of interactions between CX3CR1 and its ligands.