In clinical pharmacology studies cilazapril, after its bioactivation to cilazaprilat, was characterized as a potent, reversible angiotensin-converting enzyme (ACE) inhibitor with a terminal half-life of 30 to 50 hours consistent with saturable binding to ACE. Despite the arterial vasodilation, only slight increases in heart rate were found. Cilazapril had no acute effect on cardiovascular reflexes. Cilazapril increased effective renal plasma flow slightly. Glomerular filtration rate remained unaltered. A close and steep correlation between cilazaprilat plasma concentration and ACE inhibition was found. The potency of cilazaprilat, defined as the concentration of cilazaprilat causing 50 percent ACE inhibition, was approximately 1 ng/ml plasma. In short-term studies in hypertensive patients, it appeared that more than 90 percent of plasma ACE inhibition is needed to obtain blood pressure reduction. The result of various dose-response studies established the indirect relationship between dose, plasma concentration of the drug, and the blood pressure response and identified the dose producing maximal effect (i.e., 5 mg). Cilazapril had relatively long-lasting effects on ACE inhibition. In patients with severe chronic renal impairment or hepatic failure, the duration of ACE inhibition of cilazapril was prolonged. In these patients a reduction of the dose and/or less frequent dosing is recommended. There was no clinically relevant interaction of cilazapril with food or furosemide. The effects of hydrochlorothiazide on sodium and chloride excretion were potentiated by cilazapril. An additive effect of propranolol and nitrendipine on the blood pressure response to cilazapril was observed. An interaction with nonsteroidal anti-inflammatory drugs and cilazapril might occur, potentially reducing the blood pressure lowering effect. In general cilazapril was well tolerated.