The cerebrovascular changes that occur prior to vasovagal syncope (VVS) are unclear, with both increases and decreases in cerebrovascular resistance being reported during pre-syncope. This study assessed the cerebrovascular responses, and their potential underlying mechanisms, that occurred before VVS induced by head-up tilt (HUT). Groups of 65 normal subjects with no previous history of syncope and of 16 patients with recurrent VVS were subjected to 70 degrees HUT for up to 30 min. Bilateral middle cerebral artery (MCA) cerebral blood flow velocities (CBFVs) were measured using transcranial Doppler ultrasound, along with simultaneous measures of MCA blood pressure, heart rate, and end-tidal and transcutaneous carbon dioxide concentrations. All 16 patients and 14 of the control subjects developed VVS during HUT. During pre-syncope, mean CBFV declined, due predominantly to a decrease in diastolic rather than systolic CBFV (decreases of 44.5+/-19.8% and 6.3+/-12.9% respectively; P<0.0001). CO(2) levels and indices of cerebrovascular resistance decreased during pre-syncope, while critical closing pressure (CrCP) increased to levels approaching MCA diastolic blood pressure before decreasing precipitously on syncope. Pre-syncopal changes were similar in syncopal patients and syncopal controls. CrCP, therefore, rises during pre-syncope, possibly related to progressive hypocapnia, and may account for the relatively greater fall in diastolic CBFV. Falls in cerebrovascular resistance, therefore, may be offset by rises in CrCP due to hypocapnia, leading to diminished cerebral blood flow during pre-syncope.