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Desmopressin has been used extensively for primary nocturnal enuresis and it is associated with a low incidence of adverse effects. The only reported serious side effect is seizure or altered levels of consciousness resulting from water intoxication, which has been reported for the nasal spray. We describe 18 children with clinical symptoms of water intoxication due to the prolonged bioactivity of desmopressin nasal spray.We evaluated 18 patients with clinical suspicion of prolonged desmopressin bioactivity during treatment with intranasal desmopressin for primary nocturnal enuresis. The control group consisted of 50 children with primary nocturnal enuresis and proven nocturnal polyuria who were treated with the same desmopressin regimen.All patients had prolonged maximal urinary concentration capacity and delayed restoration of daytime diluting capacity (p <0.01). Of the patients 15 had the characteristic clinical symptoms of water intoxication with vomiting, headache, decreased consciousness and hyponatremia. We suspect that these symptoms are secondary to prolonged desmopressin bioactivity.Prolonged desmopressin bioactivity may increase the risk of water intoxication.