The purpose of this study was twofold: 1) to determine whether at high altitude cerebral blood flow (CBF) as assessed during CO2 inhalation and during hyperventilation in subjects with acute mountain sickness (AMS) was different from that in subjects without AMS and 2) to compare the CBF as assessed under similar conditions in Sherpas at high altitude and in subjects at sea level. Resting control values of blood flow velocity in the middle cerebral artery (VMCA), pulse oxygen saturation (SaO2), and transcutaneous PCO2 were measured at 4,243 m in 43 subjects without AMS, 17 subjects with AMS, 20 Sherpas, and 13 subjects at sea level. Responses of CO2 inhalation and hyperventilation on VMCA, SaO2, and transcutaneous PCO2 were measured, and the cerebral vasomotor reactivity (VMR = DeltaVMCA/PCO2) was calculated as the fractional change of VMCA per Torr change of PCO2, yielding a hypercapnic VMR and a hypocapnic VMR. AMS subjects showed a significantly higher resting control VMCA than did no-AMS subjects (74 +/- 22 and 56 +/- 14 cm/s, respectively; P < 0.001), and SaO2 was significantly lower (80 +/- 8 and 88 +/- 3%, respectively; P < 0.001). Resting control VMCA values in the sea-level group (60 +/- 15 cm/s), in the no-AMS group, and in Sherpas (59 +/- 13 cm/s) were not different. Hypercapnic VMR values in AMS subjects were 4.0 +/- 4.4, in no-AMS subjects were 5.5 +/- 4. 3, in Sherpas were 5.6 +/- 4.1, and in sea-level subjects were 5.6 +/- 2.5 (not significant). Hypocapnic VMR values were significantly higher in AMS subjects (5.9 +/- 1.5) compared with no-AMS subjects (4.8 +/- 1.4; P < 0.005) but were not significantly different between Sherpas (3.8 +/- 1.1) and the sea-level group (2.8 +/- 0.7). We conclude that AMS subjects have greater cerebral hemodynamic responses to hyperventilation, higher VMCA resting control values, and lower SaO2 compared with no-AMS subjects. Sherpas showed a cerebral hemodynamic pattern similar to that of normal subjects at sea level.