Hypothalamic pro-opiomelanocortin (POMC) neurons help regulate long-term energy stores. POMC neurons are also found in the nucleus tractus solitarius (NTS), a region regulating satiety. We show here that mouse brainstem NTS POMC neurons are activated by cholecystokinin (CCK) and feeding-induced satiety and that activation of the neuronal melanocortin-4 receptor (MC4-R) is required for CCK-induced suppression of feeding; the melanocortin system thus provides a potential substrate for integration of long-term adipostatic and short-term satiety signals.