OBJECTIVE We sought to determine whether the pressor response to an infusion of angiotensin II during pregnancy would be reduced by the oral administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E). METHODS We administered EPA-E orally to nine pregnant rabbits (200 mg/kg/day) from day 5 of gestation to day 5 postpartum. Pressor responses to graded doses of intravenously infused angiotensin II and norepinephrine were examined serially during pregnancy and the postpartum period. RESULTS The EPA-E-treated, as well as the control pregnant rabbits (n = 6), were significantly less responsive to the vasoconstrictor effects of angiotensin II throughout pregnancy than the nonpregnant rabbits (n = 8). The vascular reactivity to infused angiotensin II in EPA-E-treated pregnant rabbits, as compared with that of control pregnant rabbits was unchanged, but reactivity to angiotensin II was lower only on the fifth postpartum day. The pressor responses to infused norepinephrine were unchanged during pregnancy and in the postpartum period, and EPA-E did not alter the response. The litters of four of the nine rabbits were partially or completely macerated. CONCLUSIONS EPA-E did not reduce the already blunted pressor responsiveness to angiotensin II during pregnancy in rabbits. The effect of EPA-E in a state of increased pressor responsiveness during pregnancy due to a deficiency of vasodilatory prostaglandins needs to be determined.