THE hypothalamus plays a central role in the integrated regulation of energy homeostasis and body weight, and a number of hypothalamic neuropeptides, such as neuropeptide Y (ref. 1), galanin², CRH (ref. 3), and GLP-1 (ref. 4), have been implicated in the mediation of these effects. To discover new hypothalamic peptides involved in the regulation of body weight, we used differential display polymerase chain reaction⁵ to identify messenger RNAs that are differentially expressed in the hypothalamus of ob/+ compared with ob/ob C57B1/6J mice. We show here that one mRNA that is overexpressed in the hypothalamus of ob/ob mice encodes the neuropeptide melanin-concentrating hormone (MCH). Fasting further increased expression of MCH mRNA in both normal and obese animals. Neurons containing MCH are located in the zona incerta and in the lateral hypothalamus. These areas are involved in regulation of ingestive behaviour, but the role of MCH in mammalian physiology is unknown. To determine whether MCH is involved in the regulation of feeding, we injected MCH into the lateral ventricles of rats and found that their food consumption increased. These findings suggest that MCH participates in the hypothalamic regulation of body weight.