Fifty-five patients with mild to moderately severe essential hypertension were treated with guanabenz (2, 6-dichlorobenzylidene aminoguanidine acetate) in doses from 4 to 16 mg twice daily in a randomized, placebo-controlled study. The patients treated with placebo in the initial phase of the study were subsequently treated with guanabenz. The mean arterial pressure in the guanabenz group decreased from 130.6 to 107.6; that in the placebo group decreased from 129.6 to 126.6 standing and from 126.6 tp 109.9 and 128.8 to 120.5, respectively, supine. The principle adverse effects included sedation, dry mouth, weakness, and tiredness. Of the guanabenz-treated patients 84% had sustained decrease in supine diastolic blood pressure of 10 mm Hg or more, whereas in the placebo-treated patients only 32% had such a response. There was no significant orthostatic hypotension. Guanabenz thus appears to be an effective antihypertensive drug in patients with mild to moderately severe hypertension.