Recent evidence indicates that the hypothalamic control system of food intake involves many feeding-related neuropeptides. Melanin-concentrating hormone (MCH), one of a group of potent orexigenic peptides, is exclusively produced in neurons of the lateral hypothalamic area that give off fibers to the widespread brain regions. The receptor of MCH was recently identified to be localized in cell bodies and dendritic processes of particular neurons throughout the brain, in close spatial relation to MCH fibers. Leptin, an anorectic hormone secreted from the adipose tissue, acts on the specific receptor present on its target neurons in the brain, and suppresses the expression of both MCH and its receptor. Leptin receptor and STAT3, a transcription factor mediating the leptin signaling, are distributed in the widespread brain regions including the cerebral neocortex, hippocampal formation and lower brainstem as well as the hypothalamus where MCH fibers and the MCH receptor are abundantly present. These findings suggest that MCH exerts the effect through its specific receptor distributed throughout the brain and that the function of MCH is influenced by the condition of peripheral energy balance via leptin, the leptin receptor and STAT3, not only in the hypothalamus, but also in other brain regions. In the brain, MCH might be involved in various feeding-related functions, such as appetite, food-searching behavior, eating muscle movement, and control of energy balance, depending upon the physiological role of each region.