The localization of the melanocortin 1 (MC1) receptor in brain was investigated by in situ hybridization and immunohistochemistry. In rat periaqueductal gray matter (PAG), a small number of cells which displayed a punctate distribution showed a specific hybridization signal for MC1 receptor mRNA, whereas other regions studied were negative. In human PAG, the immunoreactivity for MC1 receptor was detected in scattered cells. These results indicate that a restricted distribution of MC1 receptor is present in the central nervous system.