The Veratran study investigated the antihypertensive efficacy of verapamil sustained release (SR) (180 mg), trandolapril (1 mg), and their fixed combination during a 24-h period. After a 4-week placebo run-in period, 272 patients (age 49 +/- 9 years, mean +/- SD) with essential hypertension and a clinic diastolic blood pressure > or =100 mm Hg were randomized to verapamil, trandolapril, their fixed combination, or placebo for 8 weeks, according to a multicenter double-blind parallel group study design. Clinic and semiautomatic blood pressure at trough and 24-h ambulatory blood pressure were measured at the end of run-in period and after 8 weeks of treatment. In the 234 patients included in the efficacy analysis, run-in clinic and semiautomatic blood pressures were reduced by verapamil, trandolapril, and combined verapamil and trandolapril significantly more than by placebo. The reductions obtained with the combination were significantly greater than those obtained by verapamil alone. Twenty-four-hour average blood pressures were not modified by placebo and were reduced by 8/6 mm Hg (systolic/diastolic) by verapamil, 11/7 mm Hg by trandolapril, and 14/11 mm Hg by the combination of the two drugs. The differences between the effect of the combination and the combination components were, in most instances, statistically significant. The verapamil-trandolapril combination was more effective also on day average blood pressure and superior to the monotherapies for the trough-to-peak ratio of the antihypertensive effect as well. Twenty-four-hour heart rate was slightly but significantly reduced by verapamil and the reduction was manifest in the group taking verapamil plus trandolapril. Thus, the antihypertensive treatment with the fixed verapamil SR-trandolapril combination is more effective and balanced over the 24 hours than the effect of the combination components administered alone.