A B S T R A C T Vascular refractoriness to the systemic pressor effects of angiotensin II (AII) develops normally during human pregnancy. To ascertain if the ewe might provide a suitable anfomal model to study the mechanisms responsible for this response (unique to pregnancy) we studied this phenomenon in unanesthetized, chronically instrumented nonpregnant and pregnant sheep, 68-143 d gestation. In these studies dose-response curves were established for changes in both mean arterial pressure and uterine blood flow. The pressor response to continuous infusions of AII increases as a function of the dose of AII in both nonpregnant and pregnant animals (P < 0.001), R = 0.943 and 0.879, respectively. However, the pregnant animals were refractory to the pressor effects ofAII, requiring 0.016 ,ug ofAll/min per kg to elicit a 20 mm Hg rise in mean arterial pressure, in contrast to 0.009 for nonpregnant animals. The slope and intercept for the regression lines are different at P < 0.001. In pregnant animals the dose-response curve for uterine blood flow was also determined. Increases in uterine blood flow were observed at doses ofAII < 0.016 ,ug/min per kg, while larger doses resulted in a progressively greater reduction in blood flow. It appears likely that the ewe may serve as an animal model suitable for the further study of the unique pregnancy-modified systemic and uteroplacental vascular responses elicited by AII.