We investigated the antihypertensive effect of the angiotensin converting-enzyme inhibitor SQ 14225 in 12 hypertensive patients for periods of three to 24 weeks. Blood pressure decreased in all patients (from 177 +/- 8/110 +/- 2 to 136 +/- 6/88 +/- 2 mm Hg--mean +/- S.E.); oral doses ranged from 400 to 1000 mg daily. Concomitant effects noted were small increases in plasma potassium concentration and pulse rate. One patient experienced a transient febrile reaction. Plasma renin activity rose during treatment, plasma aldosterone decreased, and angiotensin-converting-enzyme activity was virtually eliminated. There was no significant correlation between pretreatment plasma renin activity and degree of blood-pressure fall with SQ 14225. The exact mechanisms contributing to the blood-pressure-lowering effect of this agent remain unclear. SQ 14225 is a promising new antihypertensive agent, effective in patients refractory to traditional medical therapy.