The purpose of this study was to examine whether nociceptin/orphanin FQ (NC), the endogenous ligand of the opioid receptor-like 1 (ORL1) receptor, is able to block hypophagia induced by either stress or central administration of corticotropin releasing factor (CRF) in rats. A marked reduction in food consumption was observed following exposure to 15 min intermittent electric footshock, 60 min physical immobilization or after intracerebroventricular (i.c.v.) injection of CRF (0.1-1.0 microgram/rat). i.c.v. pretreatment with NC (0.1-2.0 micrograms/rat) completely abolished the hypophagic effect induced by stress or by i.c.v. CRF injection. The same i.c.v. doses of NC did not modify food consumption in food deprived rats and did not modify the anorexic effect induced by lipopolysaccharide, suggesting that the effect of NC is selective for anorexia induced by stress or CRF. These findings provide original evidence that NC attenuates stress-induced anorexia, presumably by acting as a functional CRF antagonist.