The comparative effects of the once a day calcium channel antagonists amlodipine and long-acting diltiazem were assessed in a parallel design, investigator-blinded, multicenter trial in 123 patients with diastolic blood pressures ranging from 95 to 114 mm Hg before treatment. Patients were randomized to one of the two drugs and titrated at 2-week intervals to 5 or 10 mg of amlodipine or 180, 240, or 360 mg of long-acting diltiazem during a 10-week treatment period. Both drugs significantly reduced resting, sitting, standing, and 24-h ambulatory systolic and diastolic pressures. Amlodipine caused significantly greater reductions in sitting and standing systolic pressures, standing diastolic pressures, and 24-h ambulatory systolic and diastolic pressures versus diltiazem. Sitting systolic pressures were reduced from 151.9 +/- 2.0 (SE) at baseline to 137.9 +/- 1.8 mm Hg with amlodipine treatment and from 149.0 +/- 2.1 to 145.1 +/- 2.5 mm Hg with diltiazem. Sitting diastolic pressures were reduced from 100.2 +/- 0.6 to 87.8 +/- 1.0 mm Hg with amlodipine and from 101.1 +/- 1.0 to 91.9 +/- 1.1 mm Hg with diltiazem. Reductions in standing systolic pressures after treatment were -12.1 +/- 1.5 mm Hg amlodipine v -4.6 +/- 1.5 mm Hg diltiazem (P < .01), and reductions in standing diastolic pressures were -11.8 +/- 0.9 mm Hg amlodipine v -8.6 +/- 0.9 mm Hg diltiazem (P < .02). Heart rates did not change significantly with either drug during the study. Two subjects in each group dropped out because of adverse experiences. Although both agents were well tolerated and reduced blood pressures consistently over the 10-week test period, amlodipine was more effective than diltiazem in reducing systolic and diastolic blood pressures to the target pressures of < 140 mm Hg systolic and < 90 mm Hg diastolic over a range of doses widely used in clinical practice.