Since Bert (1878) and Barcroft (1925), studies on hypoxia are realized by lowering ambient O(2) partial pressure (PO(2)) either by barometric pressure reduction (hypobaric hypoxia HH) or by lowering the O(2) fraction (normobaric hypoxia NH). Today, a question is still debated: "are there any physiological differences between HH and NH for the same ambient PO(2)?" Since published studies are scarce and controversial, we submitted 18 subjects in a random order to a 40-min HH test and to a 40-min NH test at an ambient PO(2) equal to 120 hPa (4500 m). Cardioventilatory variables [breathing frequency (f), tidal volume (V(t)), minute ventilation (V(E)), O(2) and CO(2) end-tidal fractions or pressures (FET(O2) and FET(CO2) or PET(O2) and PET(CO2) respectively), heart rate (HR) and O(2) arterial saturation by pulse oxymetry (SpO(2))] were measured throughout the tests. At the end of the tests, arterial blood samples were taken to measure arterial blood gases [O(2) and CO(2) arterial partial pressures ( Pa(O2) and Pa(CO2)), pH and O(2) arterial saturation (SaO(2))]. Results show that during HH compared to NH, f is greater (P</=0.001), V(t) and V(E) under BTPS conditions are lower (P</=0.05), and FET(O2) and FET(CO2) are higher (P</=0.05). However, PET(O2) does not change during the last 25 min of the tests, and neither does PET(CO2) throughout the tests. HR is higher (P</=0.05) and SpO(2) lower (P</=0.05) in HH compared to NH. Arterial blood data reveal that hypoxemia, hypocapnia and blood alkalosis are greater in HH compared to NH and that SaO(2) is lower (P</=0.05). It is concluded that the physiological responses of humans submitted to an acute hypoxia at a PO(2) equal to 120 hPa differ according to the type of hypoxia. Compared to NH, HH leads to a greater hypoxemia, hypocapnia, blood alkalosis and a lower O(2) arterial saturation. These physiological differences could be the consequence of an increase in dead space ventilation, probably related to the barometric pressure reduction, and could be grouped together under the term "the specific response to hypobaric hypoxia". Knowledge of this specific response could improve the comprehension, prevention and treatment of altitude illnesses in the future.