Objective: To evaluate the role of the arginine vasopressin (AVP)±aquaporin-2 (AQP-2) axis in the pathogenesis of nocturnal enuresis. Study participants: Twelve children (seven male and Ÿve female), aged 11X6^4X3 (6.7±15.6) years, suffering from primary monosymptomatic nocturnal enuresis and 12 healthy children, matched for sex and age. Enuretic children were further subdivided into responders and non-responders to treatment with 1-desamino-8-d-AVP (DDAVP). Methods: Serum concentrations of AVP, and plasma and urine osmolality were measured at night (0100, 0400 and 0700 h), together with nocturnal urinary excretion of AQP-2 (2000±0800 h). Magnetic resonance imaging (MRI) of the pituitary gland was carried out to evaluate the amount of AVP stored in the posthypophysis. Results: Mean AVP serum concentrations were similar in patients and controls. Urinary AQP-2 was also similar in patients and controls, but responders had a signiŸcantly lower level of AQP-2 than non-responders P , 0X005X Plasma osmolality was greater in patients than in controls P , 0X001Y whereas urinary osmolality was similar in both groups. No difference in the ratio of the signal intensity of the posterior lobe of the hypophysis to that of the pons (AVP content) was found between patients and controls or between responders and non-responders. Conclusion: A decreased urinary excretion of AQP-2 is associated with, and seems to have a role in, nocturnal enuresis, at least in some children, and this could also explain why only some of them respond to DDAVP treatment.