1 Neuropeptide Y (NPY) is one of the most potent stimulants of food intake. It has been debated which receptor subtype mediates this response. Initially Y 1 was proposed, but later Y 5 was announced as a`feeding' receptor in rats and mice. Very little is known regarding other mammals. The present study attempts to characterize the role of NPY in feeding behaviour in the distantly related guinea-pig. When infused intracerebroventricularly, NPY dose-dependently increased food intake. 2 PYY, (Leu 31 ,Pro 34 )NPY and NPY(2 ± 36) stimulated feeding, whereas NPY(13 ± 36) had no e ect. These data suggest that either Y 1 or Y 5 receptors or both may mediate NPY induced food intake in guinea-pigs. 3 The Y 1 receptor antagonists, BIBO 3304 and H 409/22 displayed nanomolar a nity for the Y 1 receptor (K i values 1.1+0.2 nM and 5.6+0.9 nM, respectively), but low a nity for the Y 2 or Y 5 receptors. When guinea-pigs were pretreated with BIBO 3304 and H 409/22, the response to NPY was inhibited. 4 The Y 5 antagonist, CGP 71683A had high a nity for the Y 5 receptor (K i 1.3+0.05 nM) without having any signi®cant activities at the Y 1 and Y 2 receptors. When CGP 71683A was infused into brain ventricles, the feeding response to NPY was attenuated. 5 The present study shows that NPY stimulates feeding in guinea-pigs through Y 1 and Y 5 receptors. As the guinea-pig is very distantly related to the rat and mouse, this suggests that both Y 1 and Y 5 receptors may mediate NPY-induced hyperphagia also in other orders of mammals.