OBJECTIVES: To elucidate the pathophysiological mechanism of the vasodepressor form (VD) of carotid sinus syndrome (CSS) by maneuvers designed to induce generalized sympathetic activation after baroreceptor unloading (lower body negative pressure, LBNP) or direct peripheral adrenoreceptor stimulation via local administration of norepinephrine (NA). DESIGN: Subjects were identified with VD of CSS through diagnostic testing. SETTING: Research laboratory. PARTICIPANTS: Eleven young controls (YC) (mean age +/- standard error of mean = 22.8 +/- 0.7), eight elderly controls (EC) (72.6 +/- 0.6), and eight elderly patients with VD (78.7 +/- 1.7). MEASUREMENTS: Forearm arterial blood flow (FABF) was measured in the left and right arms by venous occlusion plethysmography. Measurements were performed during baseline conditions, LBNP (-20 mmHg), and intra-arterial NA infusion in the left brachial artery at three progressively increasing rates (60, 120, and 240 pmol/min). RESULTS: During LBNP, FABF significantly decreased in YC (baseline 3.61 +/- 0.30 vs -20 mmHg 2.96 +/- 0.24 mL/100 g/min, P = .030) and EC (4.05 +/- 0.74 vs 3.69 +/- 0.65 mL/100 g/min, P = .033) but increased in elderly patients with VD (3.65 +/- 0.60 vs 4.54 +/- 0.80 mL/100 g/min, P = .020). During NA infusion, a significant forearm vasoconstriction occurred in YC (FABF left:right ratio 1.00 +/- 0.05 at baseline; 0.81 +/- 0.08 at 60 pmol/min, P = .034; 0.81 +/- 0.05 at 120 pmol/min, P < .001; 0.72 +/- 0.04 at 240 pmol/min, P < .001), whereas no significant FABF changes were observed in EC (1.04 +/- 0.06; 0.96 +/- 0.07, P = .655; 0.89 +/- 0.10, P = .401; 0.94 +/- 0.10, P = .590) or elderly patients with VD (1.04 +/- 0.06; 1.16 +/-0 .10, P = .117; 1.04 +/- 0.08, P = .602; 1.11 +/- 0.10, P = .305). CONCLUSION: VD of CSS is associated with a paradoxical vasodilatation during LBNP and an impairment of peripheral alpha-adrenergic responsiveness, which may be age-related.