: The indoleamine melatonin, a product of tryptophan metabolism in the pineal gland, is a free radical scavenger and antioxidant. This brief review summarizes melatonin's ability to protect nuclear DNA from oxidative damage. Using a variety of different cytogenetic, biochemical and molecular biological methods, a number of investigators have demonstrated melatonin's ability to protect DNA from the physical agent ionizing radiation, the herbicide paraquat, the carcinogen safrole, the excitotoxin kainic acid, the heavy metal chromium (VI), and a wide number of mutagens. Since these agents damage DNA because they generate free radicals, the observations are consistent with melatonin being a radical scavenger and antioxidant.