Nifedipine is a calcium-channel blocker that produces vasodilatation and decreased peripheral resistance in humans. Several clinical reports document blood-pressure-lowering effects of nifedipine with either acute or chronic administration. Little data are available to evaluate sustained-release nifedipine as a step-2 agent. We performed a multicenter double-blind, placebo-controlled trial of twice-daily nifedipine in the treatment of mild essential hypertension not controlled by diuretic alone. Seventy-one subjects completed 8 weeks of treatment with nifedipine or placebo in combination with a stable dose of diuretic. Treatment groups were comparable with respect to age, sex, race, duration of hypertension, and pretreatment weight. Baseline supine blood pressure was no different in the two treatment groups (144 +/- 15/98 +/- 6 mmHg in the nifedipine/diuretic-treated group and 145 +/- 16/98 +/- 6 mmHg in the placebo/diuretic-treated group). After 8 weeks of treatment, supine blood pressure was 132 +/- 11/88 +/- 6 mmHg in the nifedipine/diuretic-treated group and 140 +/- 16/92 +/- 8 mmHg in the placebo/diuretic-treated subjects (p less than 0.01 for both systolic and diastolic blood pressure when compared to placebo/diuretic). Nifedipine with diuretic had similar effects on standing blood pressure. Nifedipine/diuretic decreased blood pressure from baseline values within 1 week of treatment, and the effect persisted for 8 weeks. Heart rate increased in nifedipine/diuretic-treated subjects during the first 2 weeks of treatment but returned to baseline by 4 weeks. No laboratory abnormalities could be attributed to nifedipine/diuretic treatment. Side effects were mild and infrequent. In summary, nifedipine/diuretic is effective and well tolerated in the treatment of uncomplicated essential hypertension inadequately controlled with diuretic therapy alone.