Neuropeptide W (NPW) is a novel hypothalamic peptide that activates the previously described orphan G protein-coupled receptors, GPR7 and GPR8. Two endogenous molecular forms of NPW that consist of 23- and 30-amino acid residues were identified. The localization of GPR7 and GPR8 in some hypothalamic regions of primary importance in the regulation of feeding behavior has provided a springboard for investigation of the role of NPW in the central nervous system. In this study we examined the effects of NPW on feeding and energy expenditure in rats. Single intracerebroventricular (i.c.v.) administration of NPW23 and NPW30 to free-feeding rats suppressed dark phase and fasting-induced food intake at similar effective doses. Continuous i.c.v. infusion of NPW using an osmotic minipump suppressed feeding and body weight gain over the infusion period. Conversely, i.c.v. administration of anti-NPW IgG stimulated feeding. Furthermore, i.c.v. administration of NPW increased body temperature and heat production. These data raise the possibility that NPW functions as an endogenous catabolic signaling molecule in the brain. Further investigation of the biochemical and physiological functions of NPW will help us to better understand the hypothalamic regulation of energy homeostasis.