G protein-coupled receptors transduce the signal of a wide variety of hormones, neurotransmitters, cytokines, and other molecules across the cell membrane to elicit the corresponding response inside the target cells. We describe in this paper the molecular cloning and tissue distribution of a novel rat G protein-coupled receptor, GPR41, with highest homology to the human orphan G protein-coupled receptor DRY12. A lower degree of homology was seen with the receptors for bradykinin, angiotensin, and IL8. The expression of GPR41 appears to be the highest in brain and lung tissues, with lesser expression in heart, skeletal muscle, and kidney, as assayed by northern blotting. No GPR41 message was seen in spleen, liver, or testes. GPR41 failed to bind any of the ligands tested.