Guanabenz, a centrally acting antihypertensive agent that acts through stimulation of central alpha-adrenergic receptors, appears to produce neither sodium retention nor clinically significant renal, cardiac, hepatic, or metabolic abnormalities. This 2-month open, uncontrolled dose-finding and short-term safety and efficacy trial was conducted in 11 male outpatients (12 to 21 years old) to establish the potential use of guanabenz in treating children with hypertension. Doses of 3 to 12 mg/day (0.07 to 0.17 mg/kg/day) given twice daily effectively lowered blood pressure in all patients. Mean supine blood pressure was significantly (P less than 0.05) reduced from 135/91/81 mmHg (phase I/IV/V) at baseline to 124/80/66 mmHg after approximately 2 months of treatment. Mean supine pulse rate also was significantly (P less than 0.05) reduced (10 beats/minute), while standing pulse rate and body weight were unaffected by guanabenz therapy. Adverse effects, the most common being headache, dry mouth, and drowsiness, were generally mild and did not interfere with continued therapy. No abnormal findings were noted in laboratory test results or physical examinations. These preliminary results suggest that guanabenz is safe and effective for the treatment of childhood hypertension.