To evaluate the role of angiotensin II in normal man, sar1-ala8-angiotensin II (saralasin), a specific competitive inhibitor or angiotensin II, was given by graded iv infusion (1-20 microgram/kg/min over 1 h) to 6 healthy young volunteers. Significant angiotensin II-dependence of blood pressure was found only after the combined stimulus of sodium restriction (10 mEq daily for 4 days) and ambulation. Systolic blood pressure fell during saralasin infusion from 106.2 +/- 2.0 to 95.8 +/- 2.9 mm (P less than .05). At the same time, plasma renin activity rose strikingly from 3.3 +/- 0.6 to 21.6 +/- 8.5 ng/ml/h, and then fell to 9.3 +/- 4.9 over the post-infusion hour despite continued ambulation. Peak plasma renin activity correlated well with the simultaneous fall in blood pressure (r = .91; P less than .01), suggesting a compensatory response to the vascular effects of angiotensin blockaded. On an ad lib. diet, saralasin infusion had no consistent effect on plasma renin activity serum potassium, or blood pressure, but in supine volunteers plasma aldosterone increased from 9.8 +/- 2.1 to 16.5 +/- 4.8 ng/dl, an average increase of 55 +/- 17% (P less than .05). Although mena plasma cortisol decresed, individual changes in cortisol did not correlate with changes in plasma aldosterone. These data suggest that saralasin has an agonist effect on basal aldosterone secretion.