MK-801, a non-competitive NMDA receptor antagonist, enhances gastric emptying while increasing food intake. While our previously reported results implicate the vagus in MK-801's effect on feeding, it is not clear whether vagal motor fibers participate in the feeding response. Control of gastric emptying is exerted, in part, by cholinergic vagal motor neurons. Therefore, we examined the ability of MK-801 to increase meal size in the presence or absence of the muscarinic receptor antagonist, atropine methyl nitrate. Both central and systemic administration of MK-801 significantly increased intake of 15% sucrose compared to intake after NaCl injection. Intraperitoneal injection of atropine abolished the MK-801-induced increase in sucrose intake while injection of atropine into the 4^th ventricle had no effect. To determine whether augmentation of cholinergic tone produces an enhancement of food intake in the absence of MK-801, we tested the ability of cisapride, a gastric prokinetic agent that promotes acetylcholine release through an action on pre-synaptic 5-HT₄ receptors, to increase sucrose consumption. Cisapride (500 µg/kg, IP) induced a small, but significant, increase in 15% sucrose intake (15.5 ± 0.5 ml), compared to NaCl control injection (13.0 ± 0.6 ml). Furthermore, when MK-801 (100 µg/kg) was given in combination with cisapride, intake was significantly higher (19.8 ± 0.9 ml) than following either agent given alone. Pre-treatment with atropine abolished the cisapride-induced increase in intake (12.1 ± 0.9 ml) as well as the increased intake induced by combining MK-801 and cisapride. These results suggest that blockade of NMDA-gated ion channels in the hindbrain increases food intake, in part, via a peripheral muscarinic cholinergic mechanism.