Previous studies have shown the pineal hormone melatonin to influence mammalian coat color and amphibian skin color when administered exogenously. It has also been suggested that melatonin can be employed effectively to inhibit progress of neoplastic disease in both animals and humans. In the present study, we set out to investigate the effect of melatonin on human skin color in an effort to uncover its mechanism of action as an antimelanoma agent. We followed seven patients receiving orally administered melatonin over a mean duration of 19 months, and four controls who were not receiving melatonin, for an average of 12 months using monthly reflectometry measurements in three sites to determine skin color. There was no significant change in skin color among patients receiving melatonin, and no difference relative to controls. On the basis of these data, we conclude that melatonin has no effect on human skin pigmentation, and that the demonstrated effectiveness of melatonin in mediating malignant melanoma growth is not related to suppression of normal melanogenesis.