To determine whether increased vasopressinergic activity during chronic stress or adrenalectomy mediates trophic changes in the corticotroph, we examined the effect of peripheral V1 receptor blockade in rats, using the antagonist, dGly[Phaa1,D-tyr(et), Lys, Arg]VP (V1-ant), on the number of pituitary cells taking up bromo deoxy uridine (BrdU) and cells containing irACTH. Adrenalectomy significantly increased the number of BrdU- and ACTH-labeled cells at 3 and 6 days, and a much larger increase was observed at 28 days. Minipump infusion of V1-ant for 28 days, at doses blocking the increases in ACTH and corticosterone induced by exogenous VP, prevented the increases in BrdU incorporation, but not irACTH cells observed after 28 days adrenalectomy. Unexpectedly, co-localization of BrdU with ACTH positive cells was minor (about 3 cells per pituitary section) and this was unaffected by adrenalectomy or V1-antagonist infusion. In contrast, adrenalectomy for 6 or 14 days failed to increase BrdU incorporation or irACTH cells in V1b receptor knock out mice, while inducing the expected increase in wild type mice. The data shows that VP is required for pituitary mitogenesis following adrenalectomy, but at least in rats not for increasing the number of corticotrophs. The lack of co-localization of ACTH in mitotic cells suggests that recruitment of corticotrophs during adrenalectomy occurs from undifferentiated cells.