Fasting plasma renin substrate (PRS), plasma renin activity (PRA), plasma aldosterone (PA), and blood pressure (BP) levels were measured from 212 apparently healthy normotensive nonpregnant white women aged 21 to 39 years, selected on the basis of oral contraceptive (OC) use of nonuse in 1976 following a community survey in East Boston. The mean PRS level was 7118 ng/dl among OC users and 1935 ng/dl among nonusers (p less than 0.0001). In contrast, mean PRA was 2.9 ng of angiotensin 1 per milliliter per hour among users and 3.0 ng of angiotensin l/ml/hr among nonusers (p = NS); mean PA levels were 26.2 ng/dl and 25.4 ng/dl, respectively (p = NS). Mean systolic BPs were 113.8 mm Hg among current OC users and 111.2 mm Hg among nonusers (p = 0.078); diastolic BPs were 68.5 and 68.9, respectively (p = NS). These data indicate a greater than three-fold increase in PRS among current OC users compared to nonusers, with virtually identical PRA and PA levels. The data indicate that normotensive women using OCs maintain normal PRA and PA levels despite marked elevations in PRS.