Central injection of peptide YY (PYY) in sated rats produces the most powerful stimulating effect of food intake known to date. The neural mechanisms by which PYY regulates appetite are not clear but may be important because abnormal levels of PYY have been implicated in the neurobiology of bulimia nervosa. Interactions between brain acetylcholine (ACh) and PYY had not been studied. Therefore, the present experiments were designed to explore the in vivo release of ACh from the hippocampus (HPC) of rats in response to hypothalamic infusion of PYY. Hippocampal ACh release was found to increase 400% in response to 10 μg PYY. In a separate experiment, blockade of the same area of the HPC with bilateral intracerebral injections of 3.5 μg scopolamine did not affect intake stimulated by intrahypothalamic injection of 4 μg PYY. Furthermore, a third experiment showed, for the first time, that PYY (2.5-10.0 μg) can elicit robust feeding when infused directly into the HPC. The significance of these findings to the activation of limbic functions such as memory, reinforcement, and obsessional processes that accompany human binge-eating syndromes is discussed.