In 20 patients with severe hypertension, rapid oral clonidine titration was employed for control of blood pressure, with 0.2 mg as the initial dose followed by 0.2 or 0.1 mg at one hour and then 0.1 mg/hour, for a total dose of 0.8 mg. All 20 patients had a successful response, defined as a decrease in mean arterial pressure (MAP) of 30 mm Hg or more or attainment of a diastolic pressure of 100 mm Hg or lower. Baseline MAP was 160 +/- 4 (SEM) mm Hg (212 +/- 7/134 +/- 3) and decreased to 120 +/- 3 mm Hg (151 +/- 5/104 +/- 3). The mean dose was 0.32 +/- 0.02 mg, and mean response time 1.8 +/- 0.2 hours. Side effects were minimal, except for one patient who died of a cerebral infarct, which developed after the blood pressure was lowered with clonidine. Eighteen patients were treated in our emergency room; 14 were sent home after rapid titration. In ten who returned for a follow-up visit three to seven days later, blood pressure was reasonably well controlled, with clonidine and a diuretic only. Rapid oral clonidine titration can be effectively and, for the most part, safely used for treating severe hypertension even in an ambulatory setting. As with any other hypotensive drug, we recommended proceeding with caution, particularly in patients with symptomatic arteriosclerotic disease.