The safety and efficacy of sustained-release diltiazem, 120 to 180 mg twice daily, was compared with those of hydrochlorothiazide, 25 to 50 mg twice daily, in 207 patients with mild-to-moderate hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg) using a baseline, placebo, parallel-design study protocol. All patients received placebo for 2 to 4 weeks, followed by either study drug during the double-blind phase, titrated over 8 weeks to achieve a goal of supine diastolic BP reduction of at least 10 mm Hg and/or a diastolic BP of less than 90 mm Hg. Patients not achieving the treatment goal with either drug alone received the other drug in combination. Both drugs produced significant decreases in supine and upright BP throughout the 26-week study. The magnitude of decrease in mean supine diastolic BP was similar for both drugs as monotherapy at week 14 (-11.4 and -12.1 mm Hg, respectively). Hydrochlorothiazide produced significantly greater reductions at week 14 in mean supine systolic BP than sustained-release diltiazem (-19.5 and -12.7 mm Hg, respectively). The difference in mean supine diastolic BP reduction with the 2 drugs diminished when hydrochlorothiazide (50 mg/day) was compared with sustained-release diltiazem. The BP effects were sustained for 6 months with both drugs. The 2 drugs appeared to lower BP more in patients older than 60 years and more in black than in white patients. The combination of the 2 drugs decreased supine diastolic BP to goal levels in about 56% of the patients not achieving goal with either drug alone. Adverse effects were minimal with either drug alone and in combination, except for hypokalemia, which increased with thiazide alone and in combination.