Melatonin is a hormone produced and secreted by the pineal gland and known to have an important role in the regulation of mammalian reproduction. This hormone also influences circadian rhythmicity in a number of species, including humans. The regulation of melatonin production by the circadian timing system has been studied extensively as have the biochemical mechanisms in the pineal which are necessary for melatonin biosynthesis. The major enigma remaining in understanding the role of melatonin has been identification of its sites and mechanism of action. Dr. Weaver has developed and validated a quantitative autoradiographic method using an iodinated melatonin to localize its sites of action in the brain. He will use this technique to characterize the melatonin binding sites in the central nervous system and then correlate changes in binding activity within specific neuronal structures with various physiological conditions. Understanding the sites and mechanism of melatonin action has wide-ranging implications, as the hormone modulates circadian rhythmicity in humans and may be useful in treating conditions associated with abnormalities of biological rhythms, such as jet lag and depression. Furthermore, elucidating the mechanism by which melatonin regulates reproduction in animals that breed seasonally may reveal general mechanisms for the regulation of reproduction applicable to domestic farm animals. Basic research into the sites and mechanisms of melatonin action is a necessary first step towards these goals.