Maternal 1-deamino-[8-D-arginine] vasopressin (a selective antidiuretic agonist) and oral water loading decrease maternal and fetal plasma osmolality and markedly increase fetal urine flow in sheep. We hypothesized that a titrated reduction in maternal plasma osmolality would increase human amniotic fluid volume.Pregnant women (n = 5) with oligohydramnios at term were administered oral water loading (20 ml/kg) and intravenous 1-deamino-[8-D-arginine] vasopressin (2 micrograms) to induce antidiuresis. Maternal plasma and urine osmolality and urine production were measured hourly, and water replacement was titrated for 8 hours to reduce plasma osmolality by 15 to 20 mOsm/kg. The amniotic fluid index determined by ultrasonography was measured at baseline, 8 hours, and 24 hours. A control group of pregnant women (n = 5) with oligohydramnios at term was observed for 8 hours with maintenance intravenous hydration.In 1-deamino-[8-D-arginine] vasopressin-treated women, maternal urine flow increased with oral water loading, decreased with 1-deamino-[8-D-arginine] vasopressin administration, and remained reduced for 8 hours. Maternal plasma osmolality significantly decreased (285 +/- 4 to 265 +/- 4 mOsm/kg) and the amniotic fluid index significantly increased (4.1 +/- 0.6 to 8.2 +/- 1.5 cm) at 8 hours. Although maternal urine osmolality returned to basal values at 24 hours, plasma osmolality was reduced and the amniotic fluid index remained significantly increased (8.2 +/- 1.3 cm). There was no change in the amniotic fluid index (4.3 +/- 0.4 to 4.7 +/- 0.7 cm) in control patients observed with maintenance intravenous hydration.Maternal 1-deamino-[8-D-arginine] vasopressin and oral water administration can reduce and stabilize plasma osmolality and increase amniotic fluid volume. 1-Deamino-[8-D-arginine] vasopressin therapy has potential for the prevention and treatment of oligohydramnios.