After 3 weeks of placebo administration, thirty-two mildly or moderately hypertensive patients were treated with hydrochlorothiazide (HCZ) for 3 weeks, then with HCZ plus nadolol, a new beta-adrenergic blocker, for 2 years. The dose of HCZ was 50 mg once daily for all except two patients, who received 50 mg twice a day. The dose of nadolol ranged from 40 mg to 240 mg, once daily. The average supine blood pressure decreased from 182/110 mm Hg at the end of the placebo period to 170/104 mm Hg at the end of treatment with HCZ alone. Nadolol was added to the regimen, and the average supine blood pressure decreased further to 132/88 mm Hg at the end of 3 months of combined therapy. It remained essentially unchanged for the duration of the 2-year study, and no increases in the dosage of either drug were needed. Side-effects were mild, and none required a change in dosage. A once-daily dose of nadolol combined with HCZ appears to be safe and effective therapy for the long-term treatment of mild or moderate essential hypertension.