An immediate pressor response to [Sar1-Ala8]-angiotensin II (saralasin) is described in all of 16 hypertensive subjects. Blood pressure rose within 1-3 min, peaked at 4-6 min, then returned toward baseline. Plasma norepinephrine and dopamine beta-hydroxylase activity were unchanged by saralasin, indicating that the pressor response is not mediated by saralasin-induced catecholamine release. Ten normal renin hypertensives had diastolic pressor responses of 19.4 +/- 3.3 mm Hg. After 5 weeks of diuretic therapy, the diastolic pressor responses to saralasin were decreased to 4.9 +/- 2.4 mm Hg. Six low renin hypertensives had diastolic pressor responses of 26.2 +/- 6.2 mm Hg, but 5 weeks of diuretic therapy did not decrease these pressor responses significantly. In two normal and two low renin hypertensives, the diastolic blood pressure rose to levels greater than 150 mm Hg. The amplitudes of the immediate pressor responses were inversely correlated with the base-line plasma renin activities, r = -0.46. The data support the concept that the agonist activity of saralasin occurs at the angiotensin II vascular receptor level with clinical expression mediated by sodium and/or volume changes.