Because of the overexpression of the enzyme superoxide dismutase, individuals with Down syndrome (DS) are believed to suffer from increased oxidative stress as a result of the excessive production of oxygen-based free radicals; their exposure to higher than normal free radical production may account in part for signs of premature aging, early onset of cataracts, and of Alzheimer's disease. Free radicals are normally neutralized by free radical scavengers and other antioxidants. The pineal hormone melatonin is a potent scavenger of both the hydroxyl and peroxyl radicals, both of which are highly toxic, and a stimulator of the antioxidative enzyme glutathione peroxidase. Considering this, we deemed it important to define the day/night rhythm and levels of melatonin production in DS subjects. To do this, we assessed the urinary excretion of the chief melatonin metabolite, 6-hydroxymelatonin sulfate, throughout a 24 hr period in DS subjects; comparisons were made with the metabolite levels in the urine of non-Down siblings and parents of the DS subjects. All 8 non-Down subjects exhibited what was classified as normal urinary excretion of 6-hydroxymelatonin sulfate with the usual low daytime and high night-time levels of the melatonin metabolite. Of 12 DS subjects studied, 10 exhibited the normal day/night rhythm in urinary 6-hydroxymelatonin sulfate levels; 2 subjects were devoid of a rhythm. However, when all the data from each group were averaged, there were no noticeable differences in the absolute levels or 24 hr variations in urinary 6-hydroxymelatonin sulfate excretion between DS and non-Down subjects.