To evaluate the pathogenetic role of cerebral blood flow (CBF) changes occurring before and during the development of acute mountain sickness (AMS), peak mean middle cerebral artery flow velocities ([Formula: see text]) were assessed by transcranial Doppler sonography in 10 subjects at 490-m altitude, and during three 12-min periods immediately (SA₁), 3 (SA₂), and 6 (SA₃) h after decompression to a simulated altitude of 4,559 m. AMS cerebral scores increased from 0.16 ± 0.14 at baseline to 0.44 ± 0.31 at SA₁, 1.11 ± 0.88 at SA₂( P < 0.05), and 1.43 ± 1.03 at SA₃( P < 0.01); correspondingly, three, seven, and eight subjects had AMS. Absolute and relative[Formula: see text] at simulated altitude, expressed as percentages of low-altitude values (%[Formula: see text]), did not correlate with AMS cerebral scores. Average %[Formula: see text] remained unchanged, because %[Formula: see text]increased in three and remained unchanged or decreased in seven subjects at SA₂ and SA₃. These results suggest that CBF is not important in the pathogenesis of AMS and shows substantial interindividual differences during the first hours at simulated altitude.