In a double-blind study, after a four- to six-week placebo period, 418 patients with mild to moderate hypertension were randomly assigned to receive 5, 10, 20, or 40 mg of fosinopril or matched placebo orally once daily for four weeks. Seated diastolic blood pressure was determined 24 hours after the most recent dose. For patients with an inadequate blood pressure response after four weeks, doses were doubled during the second four weeks, and hydrochlorothiazide was added during the final four weeks. The patients showed a significant, consistent antihypertensive response in seated and standing systolic and diastolic blood pressures after four weeks of 20 or 40 mg of fosinopril; both dosages produced similar responses. The results indicate that the dose level of fosinopril required to treat uncomplicated mild to moderate hypertension ranges from 5 to 40 mg taken once daily. Treatment was discontinued in 3% of the fosinopril patients and in 1% of the placebo patients because of side effects. No clinically significant abnormal laboratory test results were reported. Fosinoprilat, the active diacid of fosinopril, is eliminated by both the hepatobiliary and renal routes, which suggests that fosinopril may be particularly useful in the treatment of patients with impaired kidney or liver function and of elderly patients.