The antihypertensive effects of the renin inhibitor enalkiren were compared with those of the angiotensin-converting enzyme inhibitor enalaprilat in 17 hypertensive patients (14 white, 3 black; mean age 57 years), whose renin systems had been stimulated by diuretic pretreatment. Patients were studied on 3 separate in-hospital days. On the first study day patients received placebo alone. On day 2 they received intravenous bolus doses of enalkiren (0.03 to 1.0 mg/kg), and on day 3, intravenous bolus doses of enalaprilat (0.625 to 1.25 mg). Each agent reduced systolic (p less than 0.01) and diastolic (p less than 0.01) blood pressure (BP) from baseline levels. The acute decrease in systolic BP of 18.5 +/- 0.4 mm Hg during enalkiren tended to be greater (p less than 0.01) than the decrease of 12.6 +/- 0.7 mm Hg during enalaprilat. Decreases in diastolic BP during enalkiren (11.9 +/- 0.4 mm Hg) were also slightly greater (p less than 0.1) than those during enalaprilat (9.2 +/- 0.4 mm Hg). Based on prestudy plasma renin activity (PRA), patients were divided into "high" renin (PRA greater than 3.5 ng angiotensin l/ml/hr; n = 6) and "low/normal" renin (less than 3.5 ng angiotensin l/ml/hr; n = 11) groups. Reductions in diastolic BP in the "high" renin group during enalkiren (30 +/- 5/20 +/- 3 mm Hg) tended to be greater (p less than 0.07) than those during enalaprilat (23 +/- 7/14 +/- 1 mm Hg); differences were not significant in the "low/normal" group (12 +/- 2/7 +/- 2 and 7 +/- 2/8 +/- 1 mm Hg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)