A novel G protein-coupled receptor was cloned by PCR and homology screening. Its deduced amino acid sequence is 47% identical overall to the mu, delta and kappa opioid receptors and 64% identical in the putative transmembrane domains. When transiently expressed in COS-7 cells this receptor did not bind any of the typical mu, delta or kappa opioid receptor ligands with high affinity. In situ hybridization analysis revealed that LC132 mRNA is highly expressed in several rat brain areas, including the cerebral cortex, thalamus, subfornical organ, habenula, hypothalamus, central gray, dorsal raphe, locus coeruleus and the dorsal horn of the spinal cord. Based on this distribution and its high homology with the mu, delta and kappa opioid receptors, it is proposed that LC132 is a new member of the opioid receptor family that is involved in analgesia and the perception of pain.