The rate of carbohydrate utilization during prolonged, strenuous exercise is closely geared to the energy needs of the working muscles. In contrast, fat utilization during exercise is not tightly regulated, as there are no mechanisms for closely matching availability and metabolism of fatty acids to the rate of energy expenditure. As a result, the rate of fat oxidation during exercise is determined by the availability of fatty acids and the rate of carbohydrate utilization. Blood glucose and muscle glycogen are essential for prolonged strenuous exercise, and exhaustion can result either from development of hypoglycemia or depletion of muscle glycogen. Both absolute and relative (i.e. % of maximal O2 uptake) exercise intensities play important roles in the regulation of substrate metabolism. The absolute work rate determines the total quantity of fuel required, while relative exercise intensity plays a major role in determining the proportions of carbohydrate and fat oxidized by the working muscles. As relative exercise intensity is increased, there is a decrease in the proportion of the energy requirement derived from fat oxidation and an increase in that provided by carbohydrate oxidation. During moderately strenuous exercise of an intensity that can be maintained for 90 minutes or longer ( approximately 55-75% of VO2max), there is a progressive decline in the proportion of energy derived from muscle glycogen and a progressive increase in plasma fatty acid oxidation. The adaptations induced by endurance exercise training result in a marked sparing of carbohydrate during exercise, with an increased proportion of the energy being provided by fat oxidation. The mechanisms by which training decreases utilization of blood glucose are not well understood. However, the slower rate of glycogenolysis can be explained on the basis of lower concentrations of inorganic phosphate (Pi) in trained, as compared to untrained, muscles during exercise of the same intensity. The lower Pi level is a consequence of the increase in muscle mitochondria induced by endurance exercise training. A large increase in muscle glycogen concentration, far above the level found in the well-fed sedentary state, occurs in response to carbohydrate feeding following glycogen depleting exercise. It was recently found that this muscle "glycogen supercompensation" is markedly enhanced by endurance exercise training that induces an increase in the GLUT4 isoform of the glucose transporter in skeletal muscle.