The AT1 receptor is involved in the regulation of vasopressin (VP) secretion. The effect of dehydration (2 days) on plasma and posterior pituitary (PP) VP was evaluated in the AT-1a knockout [KO(-/-)] and wild mice [KO(+/+)]. ChgBW P.Osm. P. VP PP VP Group (gram) (mOsm/kg) (pg/ml) (ng) KO(+/+)-W 0.11 ± 0.4 315.8 ± 0.8 17 ± 12 88.5 ± 4.1 KO(+/+)-D -4.21 ± 0.3 348.0 ± 4.9 49 ± 22 59.6 ± 9.8 KO(-/-)-W 0.20 ± 0.4 323.5 ± 8.0 16 ± 3 98.0 ±17.6 KO(-/-)-D -6.03 ± 1.8 388.8 ± 19.9 13 ± 5 37.6 ± 10.6 D=Dehydration, W=Water ad lib, P=Plasma, PP=Posterior Pituitary Basal levels of water intake were elevated in KO(-/-) mice [4.3 ± 03. vs. 6.5 ± 0.5 ml/24 hr; KO(+/+) vs. KO(-/-)]. There was no difference in basal levels of plasma VP and PP VP between groups. There was a greater increase in Osm and greater reduction in BW in the KO (-/-) mice. PP VP was reduced 66% in the KO (-/-) vs 32% in the wild strain. In contrast, plasma VP was increased in the KO (+/+), but not in the KO (-/-). The increased Osm coupled with PP VP depletion suggests that the AT-1a KO is hypersensitive to water restriction. The lack of change in plasma VP may be related to a depletion or fatigue of the neurosecretory system. The data provide support for a role of AT-1a receptors in the regulation of VP secretion and water balance.