In a double-blind study, patients with mild-to-moderate hypertension were randomly assigned to receive placebo or increasing daily doses of a new sustained-release formulation of diltiazem: 180 mg, 360 mg, and 540 mg, each once daily for two weeks. The numbers of evaluable patients were 26 in the placebo group and 81 in the diltiazem group at week 2, 24 and 75 at week 4, and 23 and 65 at week 6. Changes from baseline in mean supine trough (before drug administration) systolic/diastolic blood pressures were +1.3/-2.7 mmHg after placebo and -4.7/-6.1 mmHg after diltiazem at week 2; -0.1/-1.7 mmHg after placebo and -7.2/-9.3 mmHg after diltiazem at week 4; and +0.4/-1.7 mmHg after placebo and -6.7/-10.2 mmHg after diltiazem at week 6. The changes were significantly greater after diltiazem than placebo. Increasing the daily dose of diltiazem from 360 mg to 540 mg produced more than proportional increases in mean plasma diltiazem concentrations but only minimal further reductions in blood pressure. Similar rates of adverse experiences were reported by the diltiazem-treated and placebo patients. Treatment was withdrawn in two diltiazem-treated patients because of abnormal electrocardiographic (ECG) changes that were considered to be related to the drug: elevated ST segment in one and first-degree atrioventricular block in the other. No other treatment-related ECG changes were noted. It is concluded that this new once-daily formulation of diltiazem is safe and effective in the treatment of mild-to-moderate hypertension.