: About 45% of Alzheimer's disease (AD) patients have disruptions in their sleep and sundowning agitation. Since melatonin secretion is greatly inhibited in AD patients we have used melatonin to treat sleep disorders in AD patients since 1995. In a first study  we reported, in 7 out of 10 dementia patients treated with melatonin (3 mg p.o. at bed time), a decreased sundowning. In a second study  we examined 14 AD patients who received 9 mg melatonin daily for 22 to 35 months, observing a significant improvement of sleep quality with stabilization of behavioral and cognitive parameters. In a third study  we reported two monozygotic twins with AD and similar cognitive impairment, one of them receiving 6 mg melatonin at bedtime daily for 3 years. Melatonin treatment improved sleep quality and suppressed sundowning. We now report the effect of melatonin (4-month-long treatment with 6 mg/day) in 45 AD patients with sleep disturbances. Melatonin improved sleep and suppressed sundowning, an effect seen regardless of the concomitant medication employed to treat cognitive or behavioral signs of AD. Melatonin treatment seems to constitute a selection therapy to ameliorate sundowning and to slow evolution of cognitive impairment in AD patients.