Arginine vasopressin (AVP) plays a central role in water balance. In principal cells of the collecting duct system, AVP controls the expression of several genes, including aquaporin-2. Because nitric oxide (NO) participates in the regulation of water reabsorption by the collecting duct system, we analyzed the effect of AVP on the expression of NO synthase (NOS) isoforms in the kidney. Rats were either water restricted or water loaded to modify the circulating AVP levels, and expressions of NOS isoforms were assessed by Western blot analysis. In water-restricted rats, endothelial NOS (eNOS) expression increased in the outer medulla, and neuronal NOS (nNOS) expression rose in both the outer medulla and the papilla. Conversely, water loading induced a decrease in expression of nNOS in the outer medulla and papilla but did not alter eNOS expression. Oral administration of the specific V2-receptor antagonist SR-121463B decreased nNOS expression in the outer medulla and papilla but did not alter eNOS expression levels. Finally, the very low nNOS expression levels observed in AVP-deficient Brattleboro rats was restored by AVP infusion for I wk. Thus AVP specifically increases nNOS expression levels in the renal outer medulla and papilla. Because nNOS is specifically expressed in principal cells of the collecting duct system, the stimulation of nNOS expression by AVP may participate in the control of water reabsorption. principal cells; aquaporin-2; collecting duct; nitric oxide synthase