Abstract: Besides its presence in the pineal gland, melatonin has been found in a variety of other tissues as well. The indoleamine also has been identified in invertebrates including an unicellular organism where it exhibits a diurnal rhythm. Although melatonin is mainly known for its effects on seasonal reproduction and endocrine physiology, there is evidence showing that this ubiquitously acting hormone is also a potent free radical scavenger, thereby providing protection from oxidative attack to DNA and other biomolecules. Through the years, melatonin was thought to be exclusively cytosolic. However, careful examination of some of these pioneering reports revealed a nuclear localization of melatonin in different tissues including the retina and Harderian glands. Using a very sensitive immunocytochemical method, we have also found that melatonin is located in the nucleus of many cells where it may bind to nuclear components. The use of cell fractionation studies followed by radioimmunoassay confirmed these results. The administration of exogenous melatonin resulted in a marked increase in the nuclear melatonin content without a concomitant change in the cytosolic fraction. In addition to its ability to scavenge free radicals, its location in the nucleus suggests possible genomic actions.