The efficacy and safety of the antihypertensive drug, clonidine, were tested by open-label trial in 30 ambulatory, hypertensive patients who were concomitantly receiving the diuretic, chlorthalidone. This combined treatment followed several weeks of base line treatment with the diuretic alone. In both the recumbent and the upright position, clonidine potentiated the blood pressure-lowering effect of chlorthalidone alone to a noticeable degree; with combined treatment, the reductions in systolic and diastolic pressures were from 12.9% to 16.4% greater. Side-effects, consisting mostly of drowsiness and dryness of mouth, were mild and were observed mainly at the beginning of clonidine therapy. Orthostatic hypotension or weakness was experienced by 3 patients, but it subsided after dose adjustment in two of them. The drug combination was well suited for long-term management of patients with hypertension of all degrees of severity.