During orthostatic hypotension we evaluated whether presyncopal symptoms relate to a reduced brain oxygenation. Nine subjects performed 50° head-up tilt for 1 h and eight subjects were followed during 2 h of supine rest and during 1 h of 10° head-down tilt. Cerebral perfusion was assessed by transcranial Doppler determined middle cerebral artery blood velocity (MCA vmean), while brain blood oxygenation was assessed by near-infrared spectrophotometry determined concentration changes for oxygenated (ΔHbO2) and deoxygenated haemoglobin and brain cell oxygenation by the oxidized cytochrome c concentration (ΔCytO2). During head-up tilt, six volunteers developed presyncopal symptoms and mean arterial pressure (88 (78-103) to 68 (57-79) mmHg; median and range), heart rate (96 (72-111) to 65 (50-107) beats min−1), MCA vmean (59 (51-82) to 41 (29-56) cm s−1), ΔHbO2 (by −5.3 (−3.0 to −14.8) μmol l−1) and ΔCytO2 were reduced (by −0.2 (−0.1 to −0.4) μmol l−1; P < 0.05). During tilt down the cardiovascular variables recovered immediately and ΔHbO2 increased to 2.2 (−0.9-12.0) mmol L−1 above the resting value and also ΔCytO2 recovered. In the nonsyncopal head-up tilted subjects as in the controls, blood pressure, heart rate, MCA vmean and brain oxygenation indices remained stable. The results suggest that during orthostasis, presyncopal symptoms relate not only to cerebral hypoperfusion but also to reduced brain oxygenation.