Nephrogenic diabetes insipidus (NDI) is a disorder, either congenital or acquired, in which antidiuretic hormone (ADH) secretion is normal, but the ability to concentrate urine is reduced because of insensitivity of the collecting tubule to ADH. The antidiuretic action of arginine vasopressin requires binding of the hormone to the renal type V2 receptor on the basolateral membrane of the collecting duct principal cell. Binding results in activation of adenylate cyclase, generation of cAMP, and increased reabsorption of water across the apical membrane of the renal collecting duct cell. The defect in NDI may be located at any of the steps from binding of vasopressin to the final effect of the hormone on the luminal membrane.