Pituitary intermediate lobe melanocyte-stimulating hormone (MSH) is responsible for normal skin darkening in amphibians. Light-background adapted frogs (Rana pipiens) injected with naloxone and placed on black backgrounds maintain melanophore indices and pituitary cytology characteristic of light-background adaptation. In vitro and in vivo experiments showed that naloxone hydrochloride did not have a direct effect on skin melanophores or on the neurointer-mediate lobe. These data suggest that naloxone acts at the level of the central nervous system to inhibit the mechanism(s) responsible for release of MSH when light-background adapted frogs are placed on a dark background. Release of MSH, known to be tonically inhibited by the hypothalamus, may be modulated by opiate receptor-dependent mechanisms.