The biological effects of arginine vasopressin (AVP) are mediated by three receptor subtypes: the V1a and V1b receptors that activate phospholipases via Gq/11, and the V2 receptor that activates adenylyl cyclase by interacting with Gs. Isolation of the cDNAs encoding the V1a and V1b receptor subtypes explained the tissue variability of V1 antagonist binding, whereas identification of the cDNA and gene encoding the V2 receptor provided the information to identify the mutations responsible for X-linked nephrogenic diabetes insipidus. Mutations that abrogate the production and/or release of AVP from the pituitary have diabetes insipidus as their most dramatic manifestation, indicating that the maintenance of water homeostasis is the most important physiological role of this neuropeptide. Evidence for a significant role of AVP in blood pressure control, although actively sought, has been scant.