Background and Purpose We used near-infrared spectroscopy (NIRS) to monitor th Methods Fifty healthy volunteers were examined (age range, 19 to 68 years). The monitored parameters were as follows: transcranial Doppler (TCD) time-averaged middle cerebral artery how velocity end-tidal CO2 (EtCO(2)); change in concentration of cerebral oxyhemoglobin (HbO(2)), deoxyhemoglobin (Hb), and total hemoglobin; mean arterial blood pressure; peripheral arterial oxygen saturation (SaO(2)); and extracranial tissue perfusion with the use of cutaneous laser-Doppler flowmetry. The examination protocol included both hypercapnia and hypocapnia. The cerebrovascular reactivity indexes were calculated as follows: TCD, relative change in flow velocity per 1 kPa increase in EtCO(2); NIRS, absolute change in HbO(2), Hb, and total hemoglobin concentration (micromoles per liter) per 1 kPa increase in EtCO(2). Results Mean middle cerebral artery flow velocity was found to be 58 cm/s at a mean baseline EtCO(2) of 4.7 kPa. Mean cerebrovascular reactivities were as follows: TCD, 24%/kPa (SEM, 1.1); HbO(2), 2.06 mu mol/L per kilopascal (SEM, 0.08); Hb, -0.63 mu mol/L per kilopascal (SEM, 0.09): and total hemoglobin concentration, 1.44 mu mol/L per kilopascal (SEM, 0.1). Statistical analysis revealed significant correlation between reactivities calculated with the use of NIRS and TCD (P<.001). Although some fluctuations were observed in SaO(2) and laser-Doppler flux, they were not correlated with either EtCO(2) or NIRS. Conclusions NIRS signal changes in HbO(2), Hb, and total hemoglobin concentration are very sensitive to alterations in EtCO(2), which are largely independent of extracranial tissue perfusion. NIRS may be developed as an alternative method for testing cerebrovascular reactivity and may be of particular clinical importance when the ultrasound window is poor.