Cellular Po-2 as a determinant of maximal mitochondrial O-2 consumption in trained human skeletal muscle. J. Appl. Physiol. 87(1): 325-331, 1999.-Previously, by measuring myoglobin-associated Po-2 (P-MbO2) during maximal exercise, we have demonstrated that 1) intracellular Po, is 10-fold less than calculated mean capillary Po-2 and 2) intracellular Po-2 anti maximum O-2 uptake (V overdot o(2max)) fall proportionately in hypoxia. To further elucidate this relationship, five trained subjects performed maximum knee-extensor exercise under conditions of normoxia (21% Ga), hypoxia (125 O-2), and hyperoxia (100% O-2) in balanced order. Quadriceps O-2 uptake (Vo(2)) was calculated from arterial and venous blood O-2 concentrations and thermodilution blood flow measurements. Magnetic resonance spectroscopy was used to determine myoglobin desaturation, and an O-2 half-saturation pressure of 3.2 Torr was used to calculate P(Mb)o(2) from saturation. Skeletal muscle V overdot o(2max) at 12, 21, and 100% O-2 was 0.86 +/- 0.1, 1.08 +/- 0.2, and 1.28 +/- 0.2 ml.min(-1) ml-l, respectively The 100% O-2 values approached twice that previously reported in human skeletal muscle. P(Mb)o(2) values were 2.3 +/- 0.5, 3.0 +/- 0.7, and 4.1 +/- 0.7 Torr while the subjects breathed 12, 21, and 300% 0.2, respectively. From 12 to 21% O-2,V overdot o(2) and P(Mb)o(2) were again proportionately related. However, 100% O-2 increased V overdot o(2max) relatively less than P(Mb)o(2), suggesting an approach to maximal mitochondrial capacity with 100% O-2. These data 1) again demonstrate very low cytoplasmic Po-2 at V overdot o(2max), 2) are consistent with supply limitation of V overdot o(2max), of trained skeletal muscle, even in hyperoxia, and 3) reveal a disproportionate increase in intracellular Po-2 in hyperoxia, which may be interpreted as evidence that, in trained skeletal muscle, very high mitochondrial metabolic limits to muscle V overdot o(2) are being approached.