Abstract-Recent studies suggest that activation of the sympathetic nervous system either directly or indirectly influences cerebrovascular tone in humans even within the autoregulatory range. In 6 healthy subjects (aged 29Ϯ4 years), we used transcranial Doppler sonography to determine cerebral blood flow velocity during sympathetic activation elicited through head-up tilt (HUT) and sympathetic deactivation through ganglionic blockade. PaCO 2 was manipulated through hyperventilation and CO 2 breathing (5%). With subjects in the supine position and during HUT, mean arterial pressure was not influenced by PaCO 2 . During ganglionic blockade, mean arterial pressure decreased markedly with hyperventilation (Ϫ13Ϯ1.9 mm Hg). Manipulation of sympathetic tone elicited only mild changes in cerebral blood flow (64Ϯ5.8 cm/s supine, 58Ϯ4.9 cm/s upright, and 66Ϯ6.2 cm/s during ganglionic blockade; Pϭ0.07 by ANOVA). The slope of the regression between PaCO 2 and mean velocity was 1.6Ϯ0.18 cm/(s ⅐ mm Hg) supine, 1.3Ϯ0.14 cm/(s ⅐ mm Hg) during HUT, and 2.3Ϯ0.36 cm/(s ⅐ mm Hg) during ganglionic blockade (PϽ0.05). Spontaneous PaCO 2 and ventilatory response to hypercapnia were also modulated by the level of sympathetic activity. Changes in sympathetic tone have a limited effect on cerebral blood flow at normal PaCO 2 levels. However, the sympathetic nervous system seems to attenuate the CO 2 -induced increase in cerebral blood flow. This phenomenon may indicate a moderate direct effect of the sympathetic nervous system on the cerebral vasculature. Furthermore, sympathetic activation tends to increase ventilation and thus can indirectly increase cerebrovascular tone. (Hypertension. 2000;36:383-388.)Key Words: carbon dioxide Ⅲ baroreflex Ⅲ receptors, adrenergic Ⅲ phenylephrine Ⅲ sympathetic nervous system T he ability to assume the upright posture depends crucially on sufficient perfusion of the brain. 1,2 Blood flow to the brain can be influenced through adjustments in systemic hemodynamics (ie, perfusion pressure) or through local vascular modulation (ie, cerebral autoregulation). 3 Thus, impaired adjustment of systemic hemodynamics or disordered regulation of cerebrovascular tone could contribute to cerebral hypoperfusion with standing. An example of the former is the profound orthostatic hypotension seen in autonomic failure patients, which leads to cerebral hypoperfusion as the decrease in blood pressure (BP) exceeds the autoregulatory capacity of the brain. 1,4 On the other hand, the concept that impaired local regulation of cerebrovascular tone can also lead to cerebral hypoperfusion with standing is supported by recent findings in patients with orthostatic intolerance. [5][6][7][8] These patients experience typical symptoms of cerebral hypoperfusion when they stand, and these symptoms are associated with excessive reductions in cerebral blood flow velocity despite maintenance of arterial BP. 6 This cerebral vasoconstriction is attenuated either by interventions that blunt sympathetic activation or by ␣-adrenoreceptor blockad...