Acute mountain sickness (AMS) strikes those in the mountains who go too high too fast. Although AMS has been long assumed to be due solely to the hypoxia of high altitude, recent evidence suggests that hypobaria may also make a significant contribution to the pathophysiology of AMS. We studied nine healthy men exposed to simulated altitude, normobaric hypoxia, and normoxic hypobaria in an environmental chamber for 9 h on separate occasions. To simulate altitude, the barometric pressure was lowered to 432 +/- 2 (SE) mmHg (simulated terrestrial altitude 4,564 m). Normobaric hypoxia resulted from adding nitrogen to the chamber (maintained near normobaric conditions) to match the inspired PO2 of the altitude exposure. By lowering the barometric pressure and adding oxygen, we achieved normoxic hypobaria with the same inspired PO2 as in our laboratory at normal pressure. AMS symptom scores (average scores from 6 and 9 h of exposure) were higher during simulated altitude (3.7 +/- 0.8) compared with either normobaric hypoxia (2.0 +/- 0.8; P < 0.01) or normoxic hypobaria (0.4 +/- 0.2; P < 0.01). In conclusion, simulated altitude induces AMS to a greater extent than does either normobaric hypoxia or normoxic hypobaria, although normobaric hypoxia induced some AMS.