Using a degenerate PCR based approach, a fragment of the novel G protein-coupled receptor, VTR 15-20, was identified from the rat ventral tegmentum. Hybridization screening and RACE PCR were employed to isolate the full length clone. The cDNA encodes a protein of 305 amino acids which shares homology to several orphan as well as known G protein-coupled receptors. Amino acid analysis demonstrates the VTR 15-20 contains specific regions conserved among the G protein-coupled receptor superfamily. Messenger RNA encoding VTR 15-20 is expressed throughout the mammalian nervous system. Using primary rat culture systems we have demonstrated the expression of VTR 15-20 mRNA in both microglia and astrocytes. The highest levels of VTR 15-20 mRNA expression are detected in peripheral tissues including the spleen. Moreover, we have found that the expression of VTR 15-20 mRNA in brain and spleen is regulated by immunologic challenge. Based on the cellular distribution and regulation by immune challenge and neuronal insult, we hypothesize that VTR 15-20 plays a role in neuroimmune function.