OBJECTIVE Our aim was to examine changes from normal in the composition of amniotic fluid in fetal lambs with mild and severe hypoxemia and intrauterine growth restriction. METHODS Pregnant sheep underwent maternal catheterization at 88 to 93 days' gestation and fetal catheterization at 105-112 days' gestation. Twelve pregnancies (group 1) provided control data (fetal PaO 2 18-22 mm Hg), in 12 fetuses (group 2) mild hypoxemia (PaO 2 16-19 mm Hg) was induced by prevention of the normal expansion of maternal blood volume, and in 7 fetuses (group 3) chronic hypoxemia (PaO 2 12-18 mm Hg) developed spontaneously. RESULTS In group 2 amniotic fluid osmolality and sodium concentrations were lower (approximately 30 mOsm/kg and 10 mEq/L, P <.05) and urea nitrogen level was higher (10 mg/dL, P <.05) than in group 1. In group 3 osmolality and sodium concentrations at approximately 120 days' gestation were similar to those in group 1. Whereas these values decreased with gestation in groups 1 and 2 (P <.05), they remained unchanged or increased in all fetuses in group 3. Mortality rates in groups 1, 2, and 3 were 1 of 12, 4 of 12 (difference not significant), and 5 of 7 (P <.05), respectively. CONCLUSIONS Absence of normal decrease in amniotic fluid osmolality with gestation, in association with a high perinatal mortality rate, was found in severely but not in mildly hypoxemic fetuses with intrauterine growth restriction.