Increased production of superoxide and nitric oxide may produce oxidative stress in the placenta by formation of the prooxidant peroxynitrite, which itself causes vascular dysfunction. Nitrotyrosine residues, which are a marker of peroxynitrite formation and action, are found in placental vessels of preeclamptic and diabetic pregnancies, indicating oxidative stress. Treatment of the placental vasculature with authentic peroxynitrite in vitro attenuates responses both to vasoconstrictors such as the thromboxane mimetic U46619 and to vasodilators, including glyceryl trinitrate and prostacyclin, indicating it has caused vascular dysfunction. Further, the responses of the fetal-placental vasculature of diabetic and preeclamptic placentae to these same vasoconstrictor and vasodilator agents are significantly attenuated when compared to responses in normal control placentae. Together these data suggest there may be a cause and effect relationship between formation and action of peroxynitrite and vascular dysfunction in the placenta of both preeclamptic and diabetic pregnancies. The presence of such attenuated vascular responses indicates that perhaps the placenta may not be able to adequately respond to demands for altered blood flow in situations where this is necessary in preeclamptic or diabetic pregnancies, thus leading to further fetal compromise.