Mean blood flow velocity (v) of both middle cerebral arteries (MCA) was assessed by transcranial Doppler sonography (TCD) in 23 subjects at an altitude of 490 m, as well as after a rapid ascent to a high altitude research laboratory at 4559 m, and daily during a continued 72-h stay at this altitude. Relative changes of mean blood flow velocities (v) of both MCA at high altitude were expressed as percentages of low altitude values and correlated with the development of signs and symptoms of acute mountain sickness (AMS) and changes of arterial PO2, PCO2, and hemoglobin. After ascent to 4559 m, overall MCA-v (mean of all measurements obtained in each subject at high altitude) increased significantly to 148 +/- 16% of baseline values in the subjects with AMS (AMS+) and to 127 +/- 24% in the subjects without AMS (AMS-) (mean +/- SD). This v increase was higher in subjects with AMS and reached statistical significance on day 1 (+50 +/- 19%) and on day 2 (+48 +/- 23%) as compared to the healthy subjects (+27 +/- 24% and +21 +/- 26% on days 1 and 2, respectively). The rise of MCA-v correlated inversely with arterial PO2 on days 2 (r = -0.62, p < 0.005), 3 (r = -0.67, p < 0.025) and 4 (r = -0.69, p < 0.025) and from days 1 to 4 (r = -0.51, p < 0.001). MCA-v did not correlate with blood pressure, arterial PCO2 or hemoglobin. Our results suggest that subjects with AMS have a higher MCA-v increase due to a lower arterial PO2 than healthy subjects.