In a single-factor study of 24 weeks' duration with time sequence of repeated measurement, the optimal therapeutic efficacy of metoprolol as a single-dose versus twice-daily dose regimens in uncomplicated hypertensive patients was compared. Thirty moderate umcomplicated hypertensive patients with a resting supine diastolic phase-4 pressure below 120 mm Hg and a normal response to a single test dose of 100 mgm metoprolol were selected. Each patient underwent qualitative and quantitative evaluation of cardiac and pulmonary functions at 0, 2, 6, 10, 14, 18, and 24 weeks. The comparative period was divided in 3 phases according to drug regimen and differences between the two drug schedules were assessed for statistical significances using a single-factor variance/covariance model. Although therapeutically significant reduction and successful control of blood pressure was obtained under both drug regimens, the two schedules of metoprolol administered were significantly different in phase-I systolic and phase-V diastolic blood pressures. The twice-a-day schedules appeared clinically more accurate than once-a-day dosage. The present study thus emphasizes the need of 24-hour beta-adrenoceptor blockade with single-dose regimen for optimal therapeutic control of hypertension. The 24-hour beta-adrenoceptor blockade with single dose can be achieved either by the drug possessing prolonged beta-receptor affinity or with a slow-release formulation. Metoprolol used in this study, had neither prolonged beta-receptor affinity nor a slow-release formulation. Therefore, in conclusion, except for a possible benefit in terms of compliance, the once-a-day schedule of metoprolol does not provide additional interest in therapeutics.