Lactate production occurs continuously under fully aerobic conditions in intact animals, mammalian tissue preparations, intact animals, and humans in vivo. In muscles and arterial blood of resting healthy humans, lactate concentration approximates 1.0 mmol/L, while pyruvate concentration approximates 0.1 mmol/L. The lactate/pyruvate (L/P) approximates 10, with net lactate production and release from resting muscle of healthy individuals occurring when arterial partial pressure of oxygen (PO2) approximates 100 Torr and intramuscular PO2 approximates 40 Torr, well above the critical mitochondrial PO2 for maximal mitochondrial respiration (1–2 Torr).195, 196, 197 During exercise at about 65% of maximal oxygen consumption (VO2max), lactate production and net lactate release from working muscle beds rise and the L/P rises more than an order of magnitude (to approximately 500).57 However, the intramuscular PO2 remains at 3–4 Torr, well above the critical mitochondrial O2 level. Hence, it is appropriate to conclude that in healthy humans, glycolysis proceeds to lactate under fully aerobic conditions. Importantly, most (75%–80%) lactate is disposed of immediately within the tissue or subsequent to release and reuptake by working muscle, with significant uptake and oxidation by heart or oxidation by liver for gluconeogenesis. From diverse sources9,45,57,144,197,198 with permission.