This double-blind, randomized, parallel-ground study was designed to compare the efficacy of the angiotensin-converting enzyme inhibitors, trandolapril and enalapril, in 65 patients with mild to moderate primary hypertension. After a 4-week, single-blind, placebo run-in period, patients were randomized to receive either trandolapril 0.5 mg or enalapril 2.5 mg once daily. At 2-week intervals, trandolapril was titrated to 1, 2, or 4 mg and enalapril to 5, 10, or 20 mg in order to achieve a goal supine diastolic blood pressure (BP) of <90 mm Hg. In addition to casual BP measurement, 24-h ambulatory BP monitoring was performed at the end of the placebo period (baseline) and after 10 weeks of stable therapy at optimal and/or maximal dosage. Both drugs induced significant and comparable decreases in clinic systolic and diastolic BPs. The mean doses used were 3.2 mg for trandolapril and 16.6 mg of enalapril. The maximal effect was obtained at the highest dosage for both drugs in most patients with a mean decrease in supine diastolic BP of 8.6 mm Hg and 7.3 mm Hg for trandolapril 4 mg and enalapril 20 mg, respectively. Moreover, both agents significantly and similarly reduced mean 24-h as well as awake and sleep ambulatory BPs. Heart rates remained unchanged throughout the study. Our results demonstrate that both trandolapril and enalapril given at high dose exhibited significant decreases in clinic as well as in 24-h, awake, and sleep ambulatory BPs with no clear-up difference between the two treatment regimens. Moreover, our results emphasize the role of ambulatory BP monitoring when assessing the efficacy as well as the duration of action of new antihypertensive agents.