BACKGROUND Some reports claim that ventilation (VE) is greater in human subjects in normobaric hypoxia than at altitude following an equivalent drop in inspired PO2 (PIO2). It has been suggested that reduced barometric pressure (PB) may decrease chemoreceptor sensitivity and account for these results. In this pilot study we tested the hypothesis that VE and hypoxic chemoresponsiveness would not be different after 30 min of normobaric hypoxia and altitude. METHODS We exposed three male and three female subjects to four conditions in an environmental chamber, varying the order. The four conditions were: air (PB = 640, FIO2 = 0.204), hypobaria (434, 0.298), hypoxia (640, 0.141) and altitude (434, 0.203). We measured VE, end-tidal O2 and CO2 and arterial O2 saturation (SpO2) after 30 min in each environment, and while breathing 100% O2 for 1 min immediately thereafter. RESULTS The mean increase in VE relative to air was 14%, 20% and 26% for hypobaria, hypoxia and altitude, respectively, with corresponding reductions in PETCO2 in the three conditions. The reduction in VE with 100% O2 was inversely proportional to the rise in SpO2 in all cases, indicating that chemoresponsiveness was unchanged by PB. When hypobaria preceded altitude, the VE at altitude increased less, relative to air, than when altitude was given first (not significant). CONCLUSIONS The VE and chemosensitivity are about the same after 30 min of altitude and equivalent hypoxia. However, when the drop in PIO2 is not synchronous with the drop in PB, like at altitude, the VE values may be altered. Air density, hypoxic pulmonary vasoconstriction and circulating microbubbles may interact to account for the observed findings.