A peptide termed nociceptin/orphanin FQ (N/OFQ) was recently identified as an endogenous agonist for the opioid receptor-like receptor currently specified as NOP receptor. Despite many structural homologies to the opioid system, the NOP receptor shows low-affinity binding to selective opioid agonists or antagonists. Vice versa, N/OFQ selectively activates the NOP receptor but not any opioid receptor subtype. This novel receptor/ligand system is widely expressed in the brain. At the cellular level, the actions of N/OFQ resemble those elicited by opioid peptides. The NOP receptor is coupled to G-proteins, whose activation results in inhibition of adenylate cyclase, modulation of calcium and potassium conductances, and regulation of transmitter systems. At the behavioral level, systemic application of N/OFQ elicits a unique range of responses, including a wide range of effects on pain processing such as hyperalgesia, analgesia, and allodynia, as well as anxiolytic actions, modulation of opioid-mediated processes, and influences on learning and memory.