Twenty-six patients with essential hypertension were admitted to a protocol comparing the efficacy of the once-a-day administration of acebutolol with twice-a-day administration. A placebo was substituted initially for their beta-blocker therapy. Other therapy was continued in 14 (11, diuretics alone; two, diuretics plus hydralazine or alpha-methyldopa; one, alpha-methyldopa alone). After 4 weeks, lying blood pressures were 160 +/- 16 (SD) mm Hg systolic, and 101 +/- 7 mm Hg diastolic. Incremental twice-a-day doses of acebutolol resulted in normotension (lying systolic, 131 +/- 12 mm Hg; diastolic, 84 +/- 5 mm Hg) in all 26 patients (eight on 400 mg, four on 600 mg, seven on 800 mg, one on 1,000 mg, and six on 1,200 mg/day). The same twice-a-day acebutolol dose was continued for two visits, 4 weeks apart, recording pressures at 8 a.m., 12 noon, 4 p.m., and 8 p.m.; followed by two visits, 4 weeks apart, while taking the total daily dose after the 8 a.m. recording. Blood pressures during once-a-day dosing were not different from those during twice-a-day dosing at any time. Highest pressures were at 8 a.m. and lowest were at 12 noon or 4 p.m. Variations during the day in both systolic and diastolic pressures were greater during once-a-day dosing. Plasma acebutolol and metabolite concentrations were proportional to the administered dose. Eighteen patients continued acebutolol for 1 year without adverse effects other than an asymptomatic positive antinuclear antibody test in six. Once-a-day dosing was as effective as twice-a-day dosing in this group of hypertensive patients.