Opioid receptor like 1 (ORL1) receptor is a novel member of the opioid receptor family, which was not bound by any of the typical opioid receptor ligands but bound by the recently discovered nociceptin (also termed orphanin FQ) with high affinity. By using double staining of fluorescent in situ hybridization and immunohistochemistry, we observed the expression of ORL1 receptor mRNA in nociceptin-like immunoreactive neurons in multiple areas in rat brain including the hippocampus, arcuate nucleus in the hypothalamus, ventralateral periaquiductal gray (PAG) and raphe nuclei in brain stem. The expression of ORL1 mRNA in nociceptinergic neurons suggests that these receptors mediate, at least in part, the presynaptic autoreceptor functions. Further anatomical and functional significance of the autoreceptor of nociceptinergic neurons remain to be elucidated.