Following the cloning of the novel nociceptin opioid receptor (NOP(1)) and the identification of its endogenous ligand orphanin FQ/nociceptin the distribution and functional role of the NOP(1) receptor system have been studied mainly in the rodent CNS. In the present study the regional distribution and splice variant expression of the NOP(1) receptor was investigated in the adult human brain using [(3)H]-nociceptin autoradiography, NOP(1) reverse transcriptase PCR and mRNA in situ hybridization. Ligand binding revealed strong expression of functional NOP(1) receptors in the cerebral cortex and moderate signals in hippocampus and cerebellum. Interestingly, the NOP(1) receptor specific ligand was also strongly bound in the human striatum. A matching pattern of mRNA expression was observed with high amounts of NOP(1) mRNA in the prefrontal and cingulate cortex as well as in the dentate gyrus of the hippocampus. mRNA levels in the Ammon's horn and cerebellar cortex were moderate and low in the striatum. A considerable expression of N-terminal NOP(1) splice variant mRNAs was not detectable in the human brain by means of in situ hybridization. This suggests that functional NOP(1) receptors in the human brain are encoded by N-terminal full length NOP(1) transcripts. The present data on the anatomical distribution of nociceptin binding sites and NOP(1) receptor mRNA contribute to the knowledge about opioid receptor systems in the human brain and may promote the understanding of function and pharmacology of the orphanin FQ/nociceptin receptor system in the human CNS.