Introduction: We have recently reported that angiotensin II injected into the lateral brain ventricle (intracerebroventricularly, i.c.v.) increases gastric mucosal defense by elevating the level of the endogenous cannabinoid 2-arachidonoylglycerol (2-AG). The exact site of action, however, has not been elucidated yet. Since hypothalamic nuclei have been proposed to be involved in the gastro protective effect of various neuropeptides, we aimed to clarify whether the lateral hypothalamus (LH) takes part in the effect of angiotensin II and 2-AG. Methods: Gastric lesions were induced by oral injection of acidified ethanol in male Wistar rats. Angiotensin II and 2-AG were injected either i.c.v., or directly into the lateral hypothalamus 10 min before the ethanol administration in a volume of 10 or 1 microl, respectively. Results: 1. Angiotensin II injected both i.c.v. (2.8-191 pmol) and into the LH (64-191 pmol) induced gastro protective effect, with comparable potency and efficacy. 2. Similarly, 2-AG inhibited ethanol-induced mucosal damage both i.c.v. (3-26 nmol) and intrahypothalamically (6 nmol). Conclusions: Our results indicate that angiotensin II and 2AG induce central gastro protection at least partly by acting in the LH. Support: National Development Agency TAMOP-4.2.1/B-09/1/ KMR-2010, by OTKA 75965 and by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences.