Continuous positive airway pressure (CPAP) is the gold standard treatment for obstructive sleep apnea. However, the physiologic impact of CPAP on cerebral blood flow (CBF) is not well established. Ultrasound can be used to estimate CBF, but there is no widespread accepted protocol. We studied the physiologic influence of CPAP on CBF using a method integrating arterial diameter and flow velocity (FV) measurements obtained for each vessel supplying blood to the brain. FV and lumen diameter of the left and right internal carotid, vertebral, and middle cerebral arteries were measured using duplex Doppler ultrasound with and without CPAP at 15 cm H2O, applied in a random order. Transcutaneous carbon dioxide (PtcCO(2)), heart rate (HR), blood pressure (BP), and oxygen saturation were monitored. Results were compared with a theoretical prediction of CBF change based on the effect of partial pressure of carbon dioxide on CBF. Data were obtained from 23 healthy volunteers (mean +/- SD; 12 male, age 25.1 +/- 2.6 years, body mass index 21.8 +/- 2.0 kg/m(2)). The mean experimental and theoretical CBF decrease under CPAP was 12.5 % (p < 0.001) and 11.9 % (p < 0.001), respectively. The difference between experimental and theoretical CBF reduction was not statistically significant (3.84 +/- 79 ml/min, p = 0.40). There was a significant reduction in PtcCO(2) with CPAP (p = < 0.001) and a significant increase in mean BP (p = 0.0017). No significant change was observed in SaO(2) (p = 0.21) and HR (p = 0.62). Duplex Doppler ultrasound measurements of arterial diameter and FV allow for a noninvasive bedside estimation of CBF. CPAP at 15 cm H2O significantly decreased CBF in healthy awake volunteers. This effect appeared to be mediated predominately through the hypocapnic vasoconstriction coinciding with PCO2 level reduction. The results suggest that CPAP should be used cautiously in patients with unstable cerebral hemodynamics.