A variety of estrogen- and progestin-containing oral contraceptive agents reduced renal blood flow (RBF) significantly in 23 healthy, nonhypertensive young women, to a mean of 75 ± 3.3% of the value expected for their age and dietary sodium intake (P < 0.001). There was also significant activation of the renin-angiotensin system: renin substrate was increased approximately 3-fold in association with a striking increase in the circulating renin activity and angiotensin II levels in relation to sodium intake and excretion. Two observations suggest that the RBF reduction was directly mediated by angiotensin II. A correlation was demonstrable between circulating angiotensin II and RBF (P < 0.01), and renal vascular responsiveness to angiotensin II infused into the renal artery was reduced significantly (P < 0.001). Moreover, the oral contraceptive agents modified the basic relationship between sodium balance and vascular responsiveness to angiotensin II, suggesting that the agents acted through some mechanism other than alteration in the state of sodium balance. These observations provide further evidence for an important role of angiotensin 11 as a determinant of RBF. Renal vasoconstriction may contribute to the genesis of a number of complications, such as sodium retention and hypertension, associated with oral contraceptive use.