It is shown, using the computer model of glycolysis in skeletal muscle developed recently by Lambeth and Kushmerick (Ann. Biomed. Bioenerg, 30 (2001) 19-34) incorporated into the computer model of oxidative phosphorylation developed by Korzeniewski et al. (Biophys. Chem. 83 (2001) 19-34) that the regulation of glycolysis by ADP, AMP and P(i) is decidedly insufficient to explain the large increase in the glycolytic flux during transition from rest to intensive exercise in intact skeletal muscle. Computer simulations based on a simple kinetic description of the glycolytic ATP and H(+) production strongly suggests that glycolysis must be directly activated during muscle contraction. They also demonstrate that the inhibition of glycolysis by H(+) is needed to explain the transient activation of this pathway at the onset of exercise as well as the duration time and extent of the initial alkalization after the onset of exercise. Finally, it is shown that ATP supply from anaerobic glycolysis slows down the VO(2) kinetics during rest-to-work transition.