We recently isolated two orphan human G protein-coupled receptor genes designated GPR1 and GPR6. The gene GPR1 was shown to be transcribed abundantly but only in the hippocampus. Here we report the cloning of the rat GPR1 gene and report the absence of expression in hippocampus, demonstrating a functional variation for this receptor in these two species. The evolutionary history of an important sequence difference in the gene GPR1 in primate and rodent species has been examined. In contrast extensive mapping of gene GPR6 mRNA in rat brain was in keeping with the described distribution in human brain.