The increased formation of reactive oxygen species under hypoxic conditions often appears paradoxical. A prooxidant shift results from changes in cellular metabolism (especially energy metabolism), higher flux rates in catecholamine metabolism and permanent leukocyte activation. These mechanisms of increased free radical production then find themselves opposed by an antioxidant system that is markedly weakened by anemia. The erythrocytes represent an important component of the antioxidant capacity of blood, comprising in particular intracellular enzymes, e.g. superoxide dismutase and catalase, but also the glutathione system. It is thus possible that some complications of uremia are at least partly due to oxidative stress. These include cardiovascular complications, premature biological aging and increased susceptibility to infection. Strategies to strengthen the complex endogenous free radical defenses can thus be predicted to show long-term benefit. In this context the expansion of EPO therapy may well be a major step in stabilizing free radical metabolism in anemic patients.