The antihypertensive activity of cilazapril, a new nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor was evaluated in 20 outpatients (13 women, 7 men; mean age, 49 +/- 2.4 years) with mild to moderate essential hypertension, by means of an open dose-finding study of 10 weeks' duration. Cilazapril, 0.5 mg/day, was given, and the dose increased up to 10 mg/day if sitting diastolic blood pressure (SDBP) was not normalized (less than or equal to 90 mm Hg). Blood pressure measurements were carried out every 2 weeks before and 2 h after dosing. Predose and 2-h postdose measurements of plasma renin activity (PRA), angiotensin II (AII), plasma aldosterone (PA), and enzyme converting activity (ECA) were performed on the 1st day of active treatment and after 2 weeks of therapy. The SDBP decreased from 107.6 +/- 2 to 97.2 +/- 3 mm Hg 2 h after the initial dose (p less than 0.01). At the same time, ECA was inhibited 84.2 +/- 5% (p less than 0.01), AII decreased from 21.2 +/- 3 to 13.6 +/- 2 pg/ml (p less than 0.05), and PA from 208 +/- 29 to 119 +/- 14 pg/ml (p less than 0.01). After 2 weeks of therapy, ECA remained markedly reduced, by 68 +/- 6%, 24 h after the preceding cilazapril dose (p less than 0.01). The mean SDBP decreased from baseline to the end of treatment by 14.6 +/- 3 mm Hg (p less than 0.01). Cilazapril seems to be an effective antihypertensive drug which exerts potent and long-lasting ACE inhibition.