The antihypertensive and clinical effects of two centrally acting drugs, guanabenz and clonidine, were compared in a double-blind trial in 29 patients with established hypertension. After a 1-week baseline period and 2 weeks on placebo, patients received treatment with either guanabenz (mean dose 24 mg daily) or clonidine (mean dose 0.45 mg daily) alone for 8 weeks. Both drugs produced equivalent and highly significant (p < 0.001) reduction in systolic and diastolic blood pressures in the standing and supine positions. They also reduced significantly the standing and supine pulse rates. Normal orthostatic responses were maintained with both regimens. All but 1 patient in each group reported side-effects during active treatment, the most frequent being dry mouth and sedation with each drug. No laboratory or ECG abnormalities related to treatment were observed.