The . opiate receptor gene (MOR) has at least 14 exons that can generate 15 different splice variants. Recently, two new human MOR splice variants (hMOR-1O and hMOR-1X) have been identified and characterized. The two variants containing human MOR exons 1, 2, and 3 and a fourth alternative exon O, or exon X, are expressed in human brain tissue, and are selective for mu opioid binding in transfected cells. It is unclear; however, what the biologic role of these two novel human splice variants is in vivo. The mu3 opiate receptor subtype found in various human tissues where it is coupled to constitutive nitric oxide synthase derived nitric oxide release is characterized by its opiate alkaloid selectivity and its insensitivity to opioid peptides. The mu3 clone exhibits 100% identity to the mu1 receptor subtype in the center and conserved region, but with a truncated 5'-end (position 503 of mu1 mRNA) (missing several hundred nucleotides). In addition, the 3'-end of the new clone contains the 3'-end of the mu1 receptor, followed by a new fragment of 263 bases, and then by a 202 bp fragment of the 3'-end of the mu1 gene untranslated region. When mu3 is expressed in a heterologous system, the protein produced from this cDNA exhibits all of the expected biochemical characteristics of the mu3 receptor. The isolation of this novel splice variant adds support to the presence of morphinergic signaling in animals.