We analysed the importance of systemic and peripheral arteriovenous O difference (a- O and a-v O difference, respectively) and O extraction fraction for maximal oxygen uptake ( O ). Fick law of diffusion and the Piiper and Scheid model were applied to investigate whether diffusion vs perfusion limitations vary with O . Articles (n=17) publishing individual data (n=154) on O , maximal cardiac output ( ; indicator-dilution or Fick method), a- O difference (catheters or Fick equation) and systemic O extraction fraction were identified. For the peripheral responses, group-mean data (articles: n=27; subjects: n=234) on leg blood flow (LBF; thermodilution), a-v O difference and O extraction fraction (arterial and femoral venous catheters) were obtained. and two-LBF increased linearly by 4.9-6.0 L·min per 1 L·min increase in O (R =0.73 and R =0.67, respectively; both P<0.001). The a- O difference increased from 118-168 mL·L from a O of 2-4.5 L·min followed by a reduction (second-order polynomial: R =0.27). After accounting for a hypoxemia-induced decrease in arterial O content with increasing O (R =0.17; P<0.001), systemic O extraction fraction increased up to ~90% ( O : 4.5 L·min ) with no further change (exponential decay model: R =0.42). Likewise, leg O extraction fraction increased with O to approach a maximal value of ~90-95% (R =0.83). Muscle O diffusing capacity and the equilibration index Y increased linearly with O (R =0.77 and R =0.31, respectively; both P<0.01), reflecting decreasing O diffusional limitations and accentuating O delivery limitations. In conclusion, although O delivery is the main limiting factor to O , enhanced O extraction fraction (≥90%) contributes to the remarkably high O in endurance-trained individuals.This article is protected by copyright. All rights reserved.