A new antihypertensive agent, clonidine hydrochloride, was administered to 27 patients with essential hypertension for periods ranging from 4 to 18 weeks. Use of the drug in maximally tolerated doses of 0.15 to 0.9 mg daily resulted in a statistically significant reduction in average mean blood pressure (approximately 10 mm Hg) in both recumbent and standing positions. The combination of clonidine and hydrochlorothiazide produced greater reduction in supine and standing positions than either drug alone, regardless of which agent was administered first. Addition of clonidine to the regimen of patients treated with guanethidine caused a further reduction of standing, but not recumbent blood pressure. Common side effects were drowsiness, dryness of the mouth, and symptoms related to orthostasis. These side effects prevented utilization of maximally effective doses of clonidine in several patients.