The effects of the new oral converting enzyme inhibitor "MK-421" on blood pressure, plasma renin activity, plasma angiotensin II, aldosterone, and angiotensin converting enzyme were assessed in 16 hypertensive patients. Maximum (maintenance) doses ranged from 2.5 mg-40 mg daily. Blood pressure decreased from 177 +/- 7/111 +/- 4 mm Hg to 145 +/- 6/94 +/- 3 mm Hg supine and from 174 +/- 7/177 +/- 4 mm Hg to 142 +/- 6/101 +/- 3 mm Hg upright (mean +/- SEM, p less than 0.001 for both). Heart rate did not change significantly. Plasma renin activity rose during treatment, whereas plasma angiotensin II, aldosterone, and angiotensin converting enzyme remained suppressed at 24h after the maximum dose. Magnitude of blood pressure reduction after the maximum dose did not correlate with baseline plasma renin activity levels. No side-effects were noted during the 2-10 week observation period. MK-421 is similar to its predecessors in efficacy and clinical and biochemical correlates, the main difference being its higher potency and longer duration of action.