Objective: To study the relationship between changes in the cerebral blood flow (CBF) velocity with symptoms of acute mountain sickness (AMS) during simulated high altitude. Research Design and Methods: Mean middle arterial cerebral flow velocity (MCAv) was assessed by transcranial Doppler sonography in 8 healthy lowland male adults aged 20 - 24 yrs before and after 6 h and 48 h at simulated altitude corresponding to 4572 m. The same study was repeated three weeks later in the same subjects. End-tidal pCO₂ (ETCO₂) and arterial oxygen saturation (SaO₂) were measured by standardized procedures. AMS symptoms were recorded using the modified environmental symptoms questionnaire after 6 h and 48 h exposure to calculate the mean score of cerebral (AMS-C) symptoms. Results: Mean MCAv significantly increased with high altitude (HA) by 4% at 6 h HA and 24% at 48 h HA (P < 0.05) compared to sea-level values. We observed a substantial inter-subject variance in MCAv changes, especially in the first hours upon altitude exposure. Within first 2 days, we found a moderate positive correlation between MCAv with decreased ETCO₂ (mean ± SD 32 ± 4 mmHg; r = 0.47, P < 0.05), and a weak negative correlation of MCAv with a similar low SaO₂ (77% ± 8%; r = - 0.43, P < 0.05). Five of the 10 original subjects developed symptoms of AMS; however, AMS-C scores decreased (P = 0.08) with increased duration of exposure (6 h HA 0.91 ± 1.09 vs 48 h HA 0.39 ± 0.40). No differences in AMS-C scores were observed when subjects with and without increased MCAv were compared at 6 h HA and 48 h HA. Furthermore, there was no correlation between changes in neither absolute nor relative MCAv and AMS-C scores. Severity of AMS symptoms coincided well with reduction in SaO₂ (r = - 0.55, P < 0.05). Conclusion: Our results suggest that there is a lack of relationship between changes in CBF velocity with symptoms of AMS, and that a substantial inter-subject variance exists in the CBF response to high altitude exposure.