Transcranial Doppler (TCD) ultrasonography done during head-upright tilt induced neurocardiogenic syncope has demonstrated that cerebral vasoconstriction occurs concomitant with (or precedes) loss of consciousness. This article demonstrates evidence that cerebral blood flow changes alone (vasoconstriction), in the absence of systemic hypotension, may result in syncope. Five patients (4 men, 1 woman; mean age 41 +/- 17 years) with recurrent unexplained syncope were evaluated by use of an upright tilt table test for 45 minutes with or without an infusion of low dose isoproterenol. TCDoppler ultrasonography was used to assess middle cerebral artery systolic velocity (Vs); diastolic velocity (Vd); mean velocity (Vm); and pulsatility index (PI = Vs = Vd/Vmean). Syncope occurred in five patients during the baseline tilt and in one patient during isoproterenol infusion. During tilt induced syncope, at an average mean arterial pressure of 89 +/- 16 mmHg, TCD sonography showed a 2% +/- 10% increase in systolic velocity; a 51% +/- 27% decrease in diastolic velocity; and a 131% +/- 87% increase in pulsatility index. One patient underwent continuous electroencephalographic recording during tilt, which demonstrated diffuse slow wave activity (indicating cerebral hypoxia) at the time of syncope concomitant with the aforementioned TCD changes in the absence of systemic hypotension. These findings reflect an increase in cerebrovascular resistance secondary to arteriolar vasoconstriction distal to the insonation point of the middle cerebral artery, that occurred concomitant with loss of consciousness and in the absence of systemic hypotension. We conclude that in some individuals abnormal baroreceptor responses triggered during orthostatic stress may result in a derangement of cerebral autoregulation leading to cerebral vasoconstriction with resultant cerebral hypoxia in the absence of systemic hypotension.