The new renin inhibitor CGP 38560A has been shown to block angiotensin (ANG) production in healthy volunteers. In order to determine its potential antihypertensive effect, the compound was administered in a 30-min infusion, in 12 hypertensive patients (mean blood pressure (BP): 112.8 +/- 3.5 mm Hg). These patients were selected for their sensitivity to captopril: a single oral dose of 50 mg captopril lowered their mean BP by 8.8 +/- 2.2 mm Hg after 30 min and by 15.3 +/- 1.5 mm Hg after 90 min. At the end of the renin inhibitor infusion, mean blood pressure decreased by 5.7 +/- 2.2 mm Hg in the six patients infused with the dose of 0.125 mg/kg and by 6.0 +/- 1.8 mm Hg in the six patients infused with 0.250 mg/kg. The fall in blood pressure was correlated to the initial plasma renin activity (PRA) (r = 0.61, P less than .05). A dose-dependent effect was observed on plasma ANG I which fell by 74% with 0.125 mg/kg and by 94% with 0.250 mg/kg. Identical falls were found for plasma ANG II (72% and 94%, respectively) and ANG I and ANG II were well correlated (r = 0.91, P less than .001). The fall in BP was correlated to the fall in plasma ANG I (r = 0.77, P less than .01). The time-course of the BP changes was parallel to the changes in plasma angiotensins, as were the slightly delayed rise and fall in active renin measured by a direct immunoradiometric assay. When measured by the conventional ANG I radioimmunoassay, PRA values indicated a long-lasting inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)