Background and Purpose - Patients with orthostatic hypotension due to sympathetic failure become symptomatic when standing, although their capability to maintain cerebral blood flow is reported to be preserved. We tested the hypothesis that in patients with sympathetic failure, orthostatic symptoms reflect reduced cerebral perfusion with insufficient oxygen supply. Methods - This study addressed the relationship between orthostatic tolerance, mean cerebral artery blood velocity (V(mean), determined by transcranial Doppler ultrasonography), oxygenation (oxyhemoglobin [O2Hb], determined by near-infrared spectroscopy), and mean arterial pressure at brain level (MAP(MCA), determined by finger arterial pressure monitoring [Finapres]) in 9 patients (aged 37 to 70 years; 4 women) and their age- and sex-matched controls during 5 minutes of standing. Results - Supine MAP(MCA) (108±14 versus 86±14 mm Hg) and V(mean) (84±21 versus 62±13 cm ˙ s-1) were higher in the patients. After 5 minutes of standing, MAP(MCA) was lower in the patients (31±14 versus 72±14 mm Hg) as was V(mean) (51±8 versus 59±9 cm ˙ s-1), with a larger reduction in O2Hb (-11.6±4 versus - 6.7±4.5 $μ$mol ˙ L-1). Four patients terminated standing after 1 to 3.5 minutes. In these symptomatic patients, the orthostatic fall in V(mean) was greater (45±6 versus 64±10 cm ˙ s-1), and the orthostatic decrease in O2Hb (-12.0±3.3 versus -7.6±3.9 $μ$mol ˙ L-1) tended to be larger. The reduction in MAP(MCA) was larger after 10 seconds of standing, and MAP(MCA) was lower after 1 minute (25±8 versus 40±6 mm Hg). Conclusions - In patients with sympathetic failure, the orthostatic reduction in cerebral blood velocity and oxygenation is larger. Patients who become symptomatic within 5 minutes of standing are characterized by a pronounced orthostatic fall in blood pressure, cerebral blood velocity, and oxygenation manifest within the first 10 seconds of standing.