1. The hypothesis that the ventilatory resistance to O2 flow (R(V)) does limit maximal O2 consumption (V̇(O2,max)) in hypoxia, but not in normoxia, at least in non-athletic subjects, was tested. R(V) was reduced by using He-O2 mixtures. 2. V̇(O2,max) was measured during graded cyclo-ergometric exercise in eight men (aged 30 ± 3 years) who breathed N2-O2 and He-O2 mixtures in normoxia (inspired oxygen fraction (F(I,O2)) = 0.21) and hypoxia (F(I,O2) = 0.11). O2 consumption, expired and alveolar ventilations (V̇(E) and V̇(A), respectively), blood lactate and haemoglobin concentrations, heart rate and arterial oxygen saturation (S(a,O2)) were determined at the steady state of each work load. Arterial O2 and CO2 partial pressures (P(a,O2) and P(a,CO2), respectively) were measured at rest and at the end of the highest work load. 3. Maximal V̇(E) and V̇(A) were significantly increased by He-O2 breathing in normoxia (+27 and +18%, respectively), without significant changes in P(a,O2), S(a,O2) and V̇(O2,max). In hypoxia, V̇(E) and V̇(A) increased (+31 and +24%, respectively), together with P(a,O2) (+17%), S(a,O2) (+6%) and V̇(O2,max) (+14%). 4. The results support the hypothesis that the role of R(V) in limitating V̇(O2,max) is negligible in normoxia. In hypoxia, the finding that higher V̇(E) and V̇(A) values during He-O2 breathing led to higher V̇(O2,max) values suggests a greater role of R(V) as a limiting factor. It is unclear whether the finding that the V̇(O2,max) values were the same during He-O2 and N2-O2 breathing in normoxia is due to a non-linear response of the O2 transfer system, as previously proposed.
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