Maternal administration of 1-desamino-8-D-arginine-vasopressin (DDAVP) induces maternal and fetal plasma hyponatremia, accentuates fetal urine flow and increases amniotic fluid volume. Fetal hemorrhage represents an acute stress which results in fetal arginine vasopressin (AVP) secretion and reduced urine flow rate. In view of the potential therapeutic use of DDAVP for pregnancies with reduced amniotic fluid volume, we sought to examine the impact of maternal hypotonicity during acute fetal hemorrhage. Chronically catheterized pregnant ewes (130 +/-2 days) were allocated to control or to DDAVP-induced hyponatremia groups. In the latter group, tap water (2,000ml) was administered intra-gastrically to the ewe followed by DDAVP (20µg bolus, 4µg/h) and a maintenance intravenous infusion of 5% dextrose water for 4 hours to achieve maternal hyponatremia of 10-12 mEq/L. Thereafter, ovine fetuses from both groups were continuously hemorrhaged to 30% of estimated blood volume over a 60 min period. DDAVP caused similar degree of reductions in plasma sodium and osmolality in pregnant ewes and their fetuses. In response to hemorrhage, DDAVP fetuses showed greater reduction in hematocrit than control fetuses (14% vs 10%). Both groups of fetuses demonstrated similar increases in plasma AVP concentration. However, the AVP-hemorrhage threshold was greater in DDAVP fetuses (22.5%) than in control (17.5%). Hemorrhage had no significant impact on plasma osmolality, electrolyte levels or cardiovascular responses in either group of fetuses. Despite similar increases in plasma AVP, DDAVP fetuses preserved fetal urine flow rates, with values 3-fold those of control fetuses. These results suggest that under conditions of acute fetal stress of hemorrhage, maternal DDAVP may preserve fetal urine flow and amniotic fluid volume.