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.