The effects of inhibiting angiotensin converting enzyme with perindopril and aldosterone with spironolactone were tested in hypertensive patients over fifty. Accordingly, 75 patients with mild hypertension aged 50 to 70 were randomly divided into three groups for a double-blind 8 week comparison of the actions of placebo, 4 to 8 mg/day perindopril, and 37.5 to 75 mg/day spironolactone. Side-effects caused one patient to withdraw from placebo and one from spironolactone treatment. Mean blood pressure rose by 2.4 mm Hg after placebo but dropped by 7.4 and 8.6 after perindopril and spironolactone (P less than .01). Placebo, perindopril, and spironolactone did not alter blood glucose or plasma potassium, but induced, respectively, variations of -0.09, 0, and +0.34 mmol/L in cholesterol (P = .04), and -0.02, -0.05, and +0.27 mmol/L in triglycerides (P less than .01). After the three treatments, changes in angiotensin converting enzyme activity averaged -1, -6, and -1 mU/mL (P less than .01), in active renin -2, +18, and +28 pg/mL (P less than .01), and in aldosterone, +15, +8, and +95 pg/mL (P less than .01). Placebo, perindopril, and spironolactone did not alter microalbuminuria, but reduced urinary kallikrein activity by 0.9, 1.8, and 5.4 mU/mmol creatinine (P = .04). Although short-term administration of spironolactone raised renin and aldosterone markedly and lipids moderately (possibly because of volume contraction), the present results show that perindopril and spironolactone are both safe and effective for treating hypertension at the age of 50 or older.