Maternal water restriction during the last 25% of ovine gestation results in plasma hypertonicity and hypertension among 3 week old newborn lambs. We determined the cardiovascular and arginine vasopressin (AVP) responses of prenatally dehydrated (PreDehy) neonates to intravascular hemorrhage. Ewes (n=5) with singleton fetuses were water-restricted from gestation days 110 to term to achieve hypernatremia of 8-10 mEq/l. Control ewes (n=5) were provided water and food ad libitum. Immediately after delivery, ewes from both groups were provided water and food ad libitum and newborns allowed nursing ad libitum. At 15±2 d of age, PreDehy and Control lambs were prepared with bladder and femoral catheters and studied at 25±2 d of age. Following a 2-hour basal period, lambs were continuously hemorrhaged to 30% blood volume withdrawal over 1h (0.5% of blood volume/min) and were further monitored for 1h. Neonatal arterial blood samples were collected at timed intervals and arterial blood pressure was continuously monitored. During the basal period, PreDehy lambs had increased plasma sodium levels (143±1 vs 140±1 mEq/L; p<0.01), plasma osmolality (300±2 vs 293±2 mOsm/kg, p<0.01), hematocrit (26±1 vs 24±1 %, p<0.05) and mean arterial pressure (76±2 vs 66±2 mmHg, p<0.001) as compared to Controls. Both groups had similar basal arginine vasopressin (AVP) levels and heart rate. In response to hemorrhage, all parameters remained significantly elevated in PreDehy lambs. Most importantly, blood pressure decreased less in PreDehy lambs as compared to Controls. The hemorrhage-AVP threshold (% blood volume withdrawal at which plasma AVP values significantly increased) was markedly elevated (20 vs 15 %) and peak hemorrhage-induced AVP plasma levels were lower (5.6±1.5 vs 10.1±1.5 pg/ml; p<0.01) in PreDehy lambs than Controls. Thus, offspring of dehydrated ewes demonstrate enhanced AVP secretory responses to hypotension. Despite potential long term adverse effects of systemic hypertension, these results suggest a protective effect of prenatal water restriction on offspring cardiovascular homeostasis during blood volume reduction.