The purpose of this study was to determine the efficacy and safety of long-term treatment of nocturnal enuresis with desmopressin intranasal spray. Sixty-five children with primary nocturnal enuresis with a mean age of 11.3 years (range 7-17) underwent a 2-week observation period followed by dose titration period of 1 week. Those children completely dry with desmopressin entered a randomized, placebo-controlled, double-blind phase lasting 2 weeks, followed by a 6-month open treatment. The enuretic status of the children was documented for 2 weeks after the treatment was stopped. Eleven children had no change from baseline wetting with desmopressin. Thirty-two children receiving 20 mg and 9 children with 40 mg desmopressin were completely dry. Thirteen children were wet 1-2 nights per week, which was better than in the pretreatment period. During the 6-month open-treatment period, the effect of desmopressin was found to be stable. No side effects or adverse reactions were encountered. Two weeks after the treatment was stopped, 25 children were still completely dry (38% of the initial study population, 50% of the responders). The cure rate appeared to continue beyond 18 months after discontinuation of the treatment.