Pregnancy is associated with vascular refractoriness to systemic pressor responses produced by angiotensin II. The present study was designed to determine if pregnancy-induced increases in circulating levels of angiotensin II are responsible for this refractoriness. Ten ovariectomized ewes received intravenous infusions of graded doses of angiotensin II (3, 10, 30, and 100 ng/kg/min) and norepinephrine (0.1, 0.3, 1.0, and 3.0 micrograms/kg/min) prior to (control response) and during (test response) the continuous infusion of either angiotensin II (8 ng/kg/min) or norepinephrine (0.2 microgram/kg/min). Systemic pressor responses (increases in blood pressure, millimeters of mercury) to graded doses of angiotensin II were significantly depressed during the continuous angiotensin II infusion while responses to norepinephrine were not modified. In contrast, elevation of baseline levels of a second vasoconstrictor, norepinephrine, did not alter pressor responsiveness to either angiotensin II or norepinephrine. These data suggest that vascular responses to exogenously administered angiotensin II can be selectively depressed by elevated baseline levels of angiotensin II in nonpregnant sheep.