Ghrelin is a newly discovered gastric peptide, which has orexigenic effects. Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor and stimulates growth hormone and gastrointestinal motility. We have previously shown that nitric oxide (NO) plays an important role as a mediator of feeding induced by a variety of neuropeptides. This raises the question of whether ghrelin's effects are NO dependent. Here, we first determined that intracerebroventricular administration of 100 ng of ghrelin significantly increased food intake in satiated mice. We next examined the effects of N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, on ghrelin-induced increase in food intake. A subthreshold dose (12.5mg/kg; SC) of L-NAME significantly blocked the ghrelin-induced increase in food intake. Ghrelin administration increased the levels of nitric oxide synthase in the hypothalamus. This supports the hypothesis that nitric oxide is a central regulator of food consumption.