The effect of a centrally acting agent (clonidine) vs a diuretic as a single agent was studied in a group of hypertensive adolescents. Following placebo therapy, adolescents with blood pressure greater than 95th percentile were randomized to clonidine 0.1 mg or hydrochlorothiazide 25 mg, each given twice daily. Following 12 weeks' active treatment, those who had not achieved blood pressure goals proceeded to clonidine 0.2 mg or hydrochlorothiazide 50 mg twice daily. Blood pressure and clinical assessment was performed at two-week intervals. Cardiovascular response to mental stress and pre-post stress catecholamines were obtained prior to active therapy and during therapy. Clonidine therapy significantly lowered systolic and diastolic pressure and heart rate (p less than .01). Hydrochlorothiazide significantly lowered systolic pressure only. Mental stress testing resulted in a lower diastolic pressure and heart rate response (p less than .01), with lower norepinephrine in the clonidine-treated group. The diuretic group had higher plasma norepinephrine and no significant reduction in stress response. Hypertensive juveniles may be more sensitive to central control of blood pressure and more resistant to diuretics.