Progressive sympathetic activation occurs with aging. To determine the role of diminished sensitivity to central a adrenergic sympathoinhibition in the enhanced sympathetic activation seen in the elderly, we compared the effects of cumulative doses of clonidine (1, 2, and 3 µg/kg i.v.) on blood pressure and sympathetic activity in 7 healthy elderly (mean age 73±6 (SD) years) and 9 healthy young volunteers (28±9 years). Sympathetic activity was determined by measurement of norepinephrine spillover using the radioisotope dilution method. Basal plasma norepinephrine was significantly higher in elderly (276±93 pg/ml) than in young subjects (155±37 pg/ml, P <0.01). Compared to young subjects, basal norepinephrine spillover tended to be higher (0.85±0.26 vs 0.68±0.35 ng/min) and norepinephrine clearance tended to be lower (3.2±1.0 vs 4.4±1.7 L/min) in the elderly. After clonidine, both plasma norepinephrine and norepinephrine spillover decreased significantly in both elderly and in young subjects (P <0.0001) with no significant difference between the groups. The decrease in blood pressure following clonidine was also similar in elderly and young subjects. Plasma levels of clonidine did not differ significantly between the elderly and young. These findings suggest that increased sympathetic activation seen in the elderly is not due to an altered sympathoinhibitory response to a adrenergic stimulation.