The antihypertensive efficacy of combination therapy with the angiotensin-converting enzyme inhibitor captopril and a diuretic or a calcium antagonist was compared in 16 patients with essential hypertension with a blood pressure of over 160/95 mm Hg having triple drug therapy. While monotherapy with a calcium antagonist--usually verapamil 500 mg/day or nitrendipine 70 mg/day--did not reduce diastolic blood pressure to greater than 95 mm Hg, this goal was achieved in 15 out of 16 patients with the combination of captopril (53 mg/day) and the calcium antagonists in the above dose (151 +/- 4/88 +/- 2 SEM mm Hg) and in 13 out of 16 patients with captopril (84 mg/day) and a diuretic (158 +/- 4/91 +/- 1 mm Hg). There was a direct relationship between intraindividual pressure responses to the two drug combinations (r = 0.88, p less than 0.001). Heart rate was similar and weight lower on the captopril-diuretic combination. Captopril's antihypertensive efficacy can be equally enhanced by calcium antagonists (without affecting renin long term) as by diuretics, which are thought to work by stimulating the renin-angiotensin system. The calcium antagonist-captopril combination may be of particular advantage in hypertensive patients who are otherwise difficult to treat.