Glucagon-like peptide 1 (7-36)-amide (GLP-1), localized to brain areas relevant for feeding regulation, has previously been shown to potently inhibit rat feeding behavior following both intracerebroventricular injection and direct application into the paraventricular nucleus of the hypothalamus (PVN). Since third ventricular injection of GLP-1 appeared to be less effective than lateral ventricular injection, we firstly reexamined the effect of third and lateral ventricular application of GLP-1 on feeding behavior. By brain tissue mapping experiments we secondly attempted to identify brain regions other than the PVN which are sensitive towards the feeding suppressive action of exogenously injected GLP-1. And finally, microinjections of the specific GLP-1 receptor antagonist exendin (9-39)-amide were carried out into the lateral hypothalamus (LH) to determine the local role of endogenous GLP-1 in rat feeding behavior. Following lateral ventricular injection, GLP-1 significantly inhibited food intake of 24-hr fasted rats in a dose-dependent fashion with a minimal effective dose of 1 µg, which is in accord with previously published data. Moreover, following third ventricular injection, GLP-1 (1 µg) was similarly effective in suppressing food intake, which extends previous findings. Intracerebral microinjections of GLP-1 significantly suppressed food intake in the lateral hypothalamus (LH), but also in the dorsomedial (DMH) and ventromedial hypothalamus (VMH). The minimal effective dose of GLP-1 was 0.3 µg at LH injection sites and 1 µg at DMH or VMH injection sites. Feeding behavior was not significantly altered by GLP-1 in the medial nucleus of the amygdala (AMY). While the effect of endogenous GLP-1, as assessed by GLP-1 receptor blockade, has already been demonstrated for the PVN, we have further examined its role in the lateral hypothalamus. In 24-hr fasted rats, microinjections of the specific GLP-1 receptor blocker exendin (9-39)-amide into the LH at doses of 1 or 2.5 µg did not alter feeding behavior. In satiated animals, however, a single LH injection of 1 µg exendin (9-39)-amide significantly augmented food intake (0.6 vs. 0.1 g), but only during the first 20 min. With three repeated injections of 2.5 µg exendin (9-39)-amide every 20 min, 1-hr food intake was significantly increased by 300 %. Thus, the present study demonstrates that exogenous GLP-1 acts as a potent hypothalamic inhibitor of feeding behavior in rats, not only - as previously reported - in the PVN, but also in other medial hypothalamic loci as well as in the LH, where an inhibitory role of endogenous GLP-1 can be demonstrated by specific GLP-1 receptor blockade. These data strongly support and extend the concept of GLP-1 as a physiological regulator of food intake in the hypothalamus.