This prospective self-controlled study was designed to evaluate the safety and efficacy of Desmopressin (DDAVP) in the treatment of childhood primary nocturnal enuresis (PNE) and the diurnal variation of ADH secretion and urine excretion/concentration in these children. Twenty-three children (15M,8F), aged 5-16 years, who wet their beds at least 3 nights per week were enrolled in the study. After a four-week observation period, they were hospitalized for one day to monitor intake, output, renal sonography, plasma ADH, urine and serum osmolality. Intranasal DDAVP treatment at a dose of 15-30 micrograms at bedtime was started with a 4-week titration period followed by a 3 to 6-month full dose treatment period. Subsequently the dose was tapered off for one to two months, and the patients were followed for at least two months to observe any recurrence. The results showed no diurnal difference of ADH level in these children (p > 0.05); serum osmolality decreased slightly during sleep (p < 0.01); urine production decreased, and urine osmolality increased, during sleep. Seventeen children (81%) responded with a more than 50% reduction in frequency of enuresis: 11 were excellent responders, 6 were partial responders, while 4 failed. After completion of therapy, four (19%) remained dry and were considered cured; the rest had much less frequent recurrence. There were no subjective complaints other than mild local discomfort; laboratory test results remained normal. It was concluded that intranasal DDAVP is a safe and effective treatment for PNE which usually works promptly. Given the spontaneous annual remission rate of 14%, the cure rate of 19% in this study was not satisfactory.