The human AVP receptor V2 gene maps to chromosome Xq28 and is expressed in lung and kidney. Mutations in the V2 receptor result in nephrogenic diabetes insipidus (NDI), a rare X-linked disorder characterized by the inability of the kidney to concentrate urine in response to AVP. The AVP Receptor V2 activates the Gs protein and the cyclic AMP second messenger system. The AVP Receptor V3 is preferentially expressed in the pituitary and stimulates the release of adrenocorticotropic hormone (ACTH) in response to AVP by mobilizing intracellular calcium stores. AVP receptor antagonists may have potential therapeutic effects in hypertension, congestive heart failure, nephrotic syndrome and ACTH-secreting tumors.