Monozygotic twins with Alzheimer's disease of 8 years duration were studied. The onset of the disease differed by about 6 months between twins and was characterized by a primary impairment of memory function. Clinical evaluation at the time of diagnosis indicated a similar cognitive and neuroimaging alteration in both patients, as well as a similar neuropsychologic impairment. A possible genetic origin of the disease was suggested by a similar disease suffered by the mother. Patients were initially treated with vitamin E (800 I.U./day). Starting at approximately the same time (about 3 years ago), they received 50 mg/day thioridazine because of the behavioral and sleep disorder. One of the patients was treated with melatonin (6 mg orally) at bed time daily for 36 months. Evolution of the disease in the melatonin-treated patient indicated a milder impairment of memory function, with substantial improvement of sleep quality and reduction of sundowning. This led to discontinuance (after 3 months) of thioridazine treatment. Present clinical evaluation indicated a difference in functional stage of the disease between the twins (Functional Assessment Tool For Alzheimer's Disease, FAST), with a score of 5 in the twin who received melatonin and of 7b in the twin who did not receive it. Since experimental data on melatonin in animals indicated its antioxidant, antiapoptotic, and beta-amyloid-decreasing activity, the hypothesis that melatonin has a beneficial effect in Alzheimer's disease patients should be considered.