The factors limiting VO2max in humans are analyzed according to a multifactorial model derived from the O2 conductance equation. In this context, alveolar ventilation (VA) and lung O2 transfer (GL) are not considered to be limiting, at least at sea level, because changes in VA and/or in GL are not accompanied by changes in VO2max due to the shape of the O2 dissociation curve. Thus, the limits to VO2max are shared between blood O2 transport (FQ') and a peripheral factor. This last includes tissue O2 transfer (Ft') and mitochondrial O2 utilization (Fm'). In untrained subjects at sea level, blood O2 transport is found to be responsible for approximately 70% of the overall limits to VO2max (FQ' = 0.7), the rest depending on the peripheral factors. FQ', as well as the sum of Ft' and Fm', are unchanged after training or upon return to sea level following exposure to chronic hypoxia (altitude higher than 5000 m). In the latter condition, however, since tissue O2 transfer, which sets Ft', is facilitated, and mitochondrial O2 utilization, which sets Fm', is impaired, Ft' is reduced and Fm' increased as compared to control condition and/or after training.