Dutch researchers evaluated the effects of melatonin on disturbed rapid eye movement (REM) sleep in humans. A total of 14 consecutive outpatients with unselected neuropsychiatric sleep disorders and reduced REM sleep duration were included in two consecutive, randomised, double-blind, placebo-controlled, parallel-design clinical trials. Patients received 3 mg melatonin daily, administered between 2200 and 2300 h for 4 weeks. The results show that melatonin was significantly more effective than placebo: patients on melatonin experienced significant increases in REM sleep percentage and improvements in subjective measures of daytime dysfunction as well as clinical global impression score. Melatonin did not shift circadian phase or suppress temperature but did increase REM sleep continuity and promote decline in rectal temperature during sleep. These results were confirmed in patients who received melatonin in the second study (REM sleep percentage baseline/placebo/melatonin, 14.3/12.0/17.9). In patients who received melatonin in the first study and placebo in the second, the above-mentioned effects outlasted the period of melatonin administration and diminished only slowly over time.