The hypothalamic hormone vasopressin (AVP) has known mitogenic effects on various cell types. This study was designed to determine whether sustained elevated levels of circulating AVP could influence cell proliferation within adult tissues known to express different AVP receptors, including the pituitary, adrenal gland, liver and kidney. Plasmatic AVP was chronically increased by submitting animals to prolonged hyperosmotic stimulation or by implanting them with a AVP-containing osmotic minipump. After several days of either treatment, increased cell proliferation was only detected within the kidney. This kidney cell proliferation was not affected by the administration of selective V1a or V1b receptors antagonists, but was either inhibited or mimicked by the administration of a selective V2 receptor antagonist or agonist, respectively. Kidney proliferative cells mostly concerned a subpopulation of differentiated tubular cells known to express the V2 receptors and were associated with the phosphorylation of extracellular signal-regulated kinase. These data indicate that in the adult rat, sustained elevated levels of circulating AVP stimulates the proliferation of a sub-population of kidney tubular cells expressing the V2 receptor, providing the first illustration of a mitogenic effect of AVP via the activation of the V2 receptor subtype.