Melanin-concentrating hormone (MCH) is a cyclic, 19 amino acid peptide produced in the lateral hypothalamus and other regions of the mammalian brain (Bittencourt et al., 1992). When administered intracerebrally or overexpressed transgenically in rodents, MCH stimulates food intake and weight gain (Ludwig et al., 2001). Two G protein-coupled receptors for MCH, MCHR1 and MCHR2, have been identified in humans, although rodents appear only to have MCHR1 (Tan et al., 2002). Both MCHR1 and MCHR2 are expressed primarily in brain (An et al., 2001). MCHR1 has been demonstrated by genetic and pharmacological methods in rodent models to mediate obesity caused by a high fat diet or leptin deficiency (Borowsky et al., 2002; Segal-Lieberman, et al., 2003; Marsh et al., 2002). However, MCHR2 might play a similar role in the species that express it. The cloned human MCHR2-expressing cell line is made in the Chem-1 host, which supports high levels of recombinant MCHR2 expression on the cell surface and contains high levels of the promiscuous G protein Gα15 to couple the receptor to the calcium signaling pathway. Thus, the cell line is an ideal tool for screening for antagonists of interactions between MCH and MCHR2.