Nociceptin/orphanin FQ (N/OFQ) was identified in 1995 as the endogenous ligand for the orphan G i/G o-coupled opioid receptor-like 1 receptor (NOP 1). Exogenous N/OFQ increases food intake in mammals, but its effect and mode of action in chicks are not fully known. We report herein that N/OFQ (5.0 nmol) has a stimulatory effect on food intake in layer-type chicks over a 2-h period after intracerebroventricular (icv) injection. Thirty minutes after central injection of N/OFQ (5.0 nmol) the concentration of agouti-related protein (AGRP) mRNA in the diencephalon increased, while cocaine- and amphetamine-regulated transcript (CART) mRNA decreased. However, concentrations of neuropeptide Y, proopiomelanocortin and glutamate decarboxylase mRNAs, and of catecholamines and excitatory amino acids were not affected. Simultaneous administration of α-melanocyte stimulating hormone (α-MSH: 1.0 pmol), a competitor of AGRP, completely blocked the orexigenic effect of N/OFQ (5.0 nmol). These data suggest that N/OFQ functions in layer chicks as an orexigenic peptide in the central nervous system, and that the AGRP and the CART neurons may mediate this function, as in mammals.