Once-daily antihypertensive drugs that control blood pressure (BP) for the full 24-h dosing period, enhance patient compliance and may reduce the cardiovascular complications of hypertension which occur with increased frequency in the early morning. Since some once-daily agents are more effective than others in maintaining antihypertensive effects toward the end of the 24-h dosing interval this study was designed to evaluate the duration of antihypertensive action of trandolapril using 48 h ambulatory blood pressure monitoring (ABPM) in 41 patients with mild-to-moderate essential hypertension. Twenty-four hour ABPM was performed on two consecutive days (48 h) after a 4 week single blind placebo run-in period and repeated after an 8 week double-blind period during which 20 patients were randomized to treatment with trandolapril (2-4 mg once-daily) and 21 patients to matching placebo. During the second 48 h monitoring period, placebo rather than active medication was taken by both of the groups at the beginning of the second 24 h segment. Trandolapril reduced ambulatory systolic and diastolic BP by 9.4 and 6.2 mm Hg respectively (P < or = 0.01) during the first 24 h of the post treatment monitoring period while placebo increased the systolic and diastolic BPs in the same period by 3.8 and 2.6 mm Hg (P < 0.05). During the second monitoring period (hours 25-48), trandolapril reduced systolic and diastolic BP by 5.6 and 3.9 mm Hg while placebo increased BP by 2.3 and 1.6 mm Hg (P < 0.03). When compared to placebo by 2 h time blocks, throughout the 2 days of monitoring, trandolapril produced clinically significant decreases in systolic and diastolic BP for 30 and 28 h following dosing. This indicates that trandolapril can be considered a true once-daily antihypertensive agent.