Skeletal muscle adapts to endurance exercise, such as long distance running, with an increase in the capacity for aerobic metabolism. This is reflected in an increased capacity of whole homogenates and of the mitochondrial fraction of muscle to oxidize pyruvate and long chain fatty acids. Underlying this increase in the ability to obtain energy by respiration is an increase in the levels of a number of mitochondrial enzymes. These include the enzymes involved in fatty acid oxidation, the enzymes of the citric acid cycle, the components of the respiratory chain that link the oxidation of succinate and NADH to oxygen, and coupling factor 1. These increases in mitochondrial enzyme activity appear to be due to an increase in enzyme protein as evidenced by a doubling of the concentration of cytochrome c and a 60% increase in the protein content of the mitochondrial fraction of skeletal muscle. Electronmicroscopic studies suggest that increases in both the size and number of mitochondria are responsible for the increase in mitochondrial protein. An alteration in mitochondrial composition also occurs, with some mitochondrial enzymes increasing 2-fold, others increasing only 35% to 60%, while others, including mitochondrial α-glycerophosphate dehydrogenase, creatine phosphokinase and adenylate kinase do not increase at all. As a result of these and other exercise induced biochemical adaptations skeletal muscle tends to become more like heart muscle in its enzyme pattern.