In order to evaluate the antihypertensive effect and the tolerability of combination therapy with an angiotensin converting enzyme inhibitor (captopril) and a dihydropyridine calcium antagonist (nifedipine) compared with monotherapy and placebo, we studied 32 uncomplicated essential hypertensives. At the end of a 1-month placebo washout period, their diastolic blood pressure was greater than 105 and less than 120 mmHg. The subjects then received, according to a double-blind randomized crossover design, captopril (50 mg twice daily), nifedipine (20 mg twice daily), captopril plus nifedipine at the same doses and the corresponding placebo, each treatment being given for 1 month. Both captopril and nifedipine significantly reduced mean blood pressure, which was further and significantly reduced by the combination of the two drugs. The decreases in mean blood pressure induced by nifedipine were significantly greater than those induced by captopril, and those induced by the combined therapy were significantly greater than those induced by either drug on monotherapy. The heart rate was significantly increased only by nifedipine, and to a similar, but not significant, extent by the combination therapy. Plasma renin activity was similarly and significantly increased and urinary aldosterone tended to decrease to a similar extent under the three active treatments. Adverse effects were mild to moderate in intensity; their incidence under captopril was lower than that under placebo, while the incidence under nifedipine and combined therapy was greater than under placebo. Ankle oedema disappeared under the combined therapy in three out of four patients who developed this side effect under nifedipine, although one additional patient developed ankle oedema under combination therapy.(ABSTRACT TRUNCATED AT 250 WORDS)