Increase in fetoplacental vascular resistance caused by hypoxia is considered one of the key factors of placental hypoperfusion and fetal undernutrition leading to intrauterine growth restriction (IUGR), one of the serious problems in current neonatology. However, although acute hypoxia has been shown to cause fetoplacental vasoconstriction, the effects of more sustained hypoxic exposure are unknown. This study was designed to test the hypothesis that chronic hypoxia elicits elevation in fetoplacental resistance, that this effect is not completely reversible by acute re-oxygenation, and that it is accompanied by increased acute vasoconstrictor reactivity of fetoplacental vasculature. We measured fetoplacental vascular resistance, as well as acute vasoconstrictor reactivity, in isolated perfused placentae from rats exposed to hypoxia (10% O₂) during the last week of a 3-week pregnancy. We found that chronic hypoxia shifted the relationship between perfusion pressure and flow rate towards higher pressure values (by ~20%). This increased vascular resistance was refractory to a high dose of sodium nitroprusside, implying involvement of other factors than increased vascular tone. Chronic hypoxia also increased vasoconstrictor responses to angiotensin II (by ~75%) and to acute hypoxic challenges (by >150%). We conclude that chronic prenatal hypoxia causes a sustained elevation of fetoplacental vascular resistance and vasoconstrictor reactivity that are likely to produce placental hypoperfusion and fetal undernutrition in vivo.