The effect of labetalol on blood pressure, heart rate and the renin-angiotensin system was evaluated in 12 patients with severe essential hypertension (diastolic blood pressure greater than or equal to 120 mmHg, WHO: Phase I and II) who had been resistant to other therapeutic regimens. In 9 (76%) patients, labetalol produced a marked reduction in systolic and diastolic pressure (p less than 0.001), while the other 3 patients required the combination of high doses of the drug (1600 mg/day) with a diuretic to achieve normal blood pressure levels. The average dose which controlled blood pressure levels was 777 +/- 393 mg/day. Treatment produced a progressive decrease in heart rate. Side-effects were transient. In contrast to other beta-adrenergic blockers, treatment with labetalol did not modify plasma renin activity levels nor the total concentration of renin or inactive renin levels. During the 1-year follow-up none of the patients treated with labetalol developed cardiovascular accidents, while 4 cardiovascular events occurred in a group of 12 age-matched non-treated severely hypertensive patients. The results of this study indicate that labetalol, administered as a single therapy or in combination with a diuretic, can control blood pressure levels in severely hypertensive patients who had been resistant to the administration of other therapies. Its effects on blood pressure are not related to the renin-angiotensin system.