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Purpose: Monosymptomatic nocturnal enuresis is a disorder, the precise etiology and pathomechanism of which remain unknown. An elevated sleep arousal threshold leading to deep sleep, and an amplitude disturbance in circadian arginine vasopressin secretion and urine production have been suggested as possible causes of the disease. The pineal hormone melatonin is allegedly implicated in the physiological sleep mechanism and circadian system. Melatonin serum levels are high at night and low during the day. The major metabolite of melatonin, 6-hydroxy-melatonin-sulfate (aMT6s), is excreted in the urine and is a good indicator of its production. We explore whether alterations in melatonin secretion assessed by its aMT6s excretion might be implicated in the pathomechanism of monosymptomatic nocturnal enuresis., Materials and Methods: Urine was collected for 24-hour periods from 44 children with monosymptomatic nocturnal enuresis, 10 children with other forms of enuresis/incontinence (nonmonosymptomatic nocturnal enuresis) and 25 controls, and its aMT6s concentration was estimated using a commercially available radioimmunoassay. The total amount of aMT6s excreted per day was calculated., Results: We found no significant differences in the amount of aMT6s excreted in a 24-hour period among patients with or without monosymptomatic nocturnal enuresis and controls with values of 17.6 microg. (1st to 3rd percentile 10.0 to 27.8) versus 13.4 (9.1 to 19.6) versus 21.5 (13.5 to 31.4), respectively. If aMT6s excretion was related to body weight, the result did not change., Conclusions: Our data do not indicate that alterations in melatonin production might be involved in the elevation of the sleep arousal threshold associated with deep sleep in children with monosymptomatic nocturnal enuresis.