To test the hypothesis that the combination of a calcium antagonist and diuretic is less effective in lowering BP than the combination of ACE inhibitor plus diuretic, we compared two groups of patients. The first was a group of 157 consecutive patients (32% male, 90% black, aged 57 +/- 1 years) in whom the only change in therapy was the addition or deletion of either a calcium antagonist or diuretic. Each patient served as his/her own control, with a follow-up time of 41 +/- 4 days. The BP responses of this group were compared with those of another group of 170 consecutive patients (33% male, 85% black, aged 55 +/- 1 years), who had had the addition or deletion of an ACE inhibitor or diuretic some 32 +/- 2 days previously. As there were no statistically significant differences either between drugs within the classes or between the addition or deletion of a drug, the BP results were pooled. Combination therapy with calcium antagonist + diuretic was associated with a 13.4 +/- 1.7/5.4 +/- 0.9 mmHg drop in supine BP; the ACE inhibitor + diuretic combination lowered supine BP by 12.3 +/- 1.6/8.0 +/- 0.9 mmHg compared with monotherapy (all P less than 0.001 by paired t-test). The effects on standing BP were similar: calcium antagonist + diuretic, 13.2 +/- 1.9/5.6 +/- 0.9 mmHg; and ACE inhibitor + diuretic, 12.3 +/- 1.5/7.0 +/- 0.9 mmHg (all P less than 0.001). There were no significant differences in BP responses between the calcium antagonist + diuretic and ACE inhibitor + diuretic combinations. These data indicate that, regardless of the order of addition or subtraction, the combination of calcium antagonist + diuretic was more effective in lowering BP than either agent used alone, and that the combination of calcium antagonist + diuretic was as effective as the ACE inhibitor + diuretic combination.