A double-blind multicenter study compared oral acebutolol (n = 182) with hydrochlorothiazide (n = 178) in the treatment of mild to moderate essential hypertension (diastolic blood pressure 95 to 114 mm Hg). Both agents produced significant and comparable reductions in systolic, diastolic, and mean arterial blood pressures of 15.9, 14.9, and 15.3 mm Hg on acebutolol, and 15.2, 13.3, and 11.8 mm Hg on hydrochlorothiazide (p = 0.001). Acebutolol induced a significant reduction in resting heart rate of 9.3 bpm (p = 0.001) from baseline. The mean effective doses of acebutolol and hydrochlorothiazide were 757 and 68 mg, respectively. Significantly fewer patients on acebutolol experienced arrhythmia, anorexia, and flatulence, although an equal number of patients (14) in each group discontinued therapy prematurely due to side effects. More hydrochlorothiazide-treated patients developed abnormalities in the levels of serum glucose, uric acid, blood urea nitrogen (BUN), serum potassium, and chloride. No clinically significant trends in laboratory parameters were seen on acebutolol, although a small number of patients (11 on acebutolol and 3 on hydrochlorothiazide) developed asymptomatic positive antinuclear antibody (ANA) tests of low titer. The data show that acebutolol is as effective as hydrochlorothiazide in the treatment of hypertension, is as well tolerated, and produces fewer biochemical abnormalities.