The biochemical mechanisms behind skeletal muscle soreness and damage with muscular overuse have remained unclear. Recently, however, a growing amount of evidence indicates that free radicals play an important role as mediators of skeletal muscle damage and inflammation. During exercise, two of the potentially harmful free radical generating sources are semiquinone in the mitochondria and xanthine oxidase in the capillary endothelial cells. During high intensity exercise the flow of oxygen through the skeletal muscle cells is greatly increased at the same time as the rate of ATP utilisation exceeds the rate of ATP generation. The metabolic stress in the cells causes several biochemical changes to occur, resulting in a markedly enhanced rate of production of oxygen free radicals from semiquinone and xanthine oxidase. During normal conditions free radicals are generated at a low rate and subsequently taken care of by the well developed scavenger and antioxidant systems. However, a greatly increased rate of free radical production may exceed the capacity of the cellular defence system. Consequently, a substantial attack of free radicals on the cell membranes may lead to a loss of cell viability and to cell necrosis and could initiate the skeletal muscle damage and inflammation caused by exhaustive exercise.