Erythropoietin (EPO) has proven to be effective in the treatment of anemia caused by chronic renal failure (CRF). Though such treatment does improve the quality of life, peak oxygen uptake after EPO therapy does not improve as much as one would predict given the increase in hemoglobin concentration. We predicted that uremic myopathy provokes a cytosolic dysfunction without altering mitochondrial oxidative capacity. To test this hypothesis, we tested six CRF patients and six matched sedentary normals here and at the University of Barcelona. We found no mitochondrial differences between the two groups. However, the oxygen gradients from capillary to muscle cell were higher in the CRF group, while peak oxygen uptake was reduced. Moreover, the transcapillary gradient and oxygen uptake levels for the CRF group breathing 100% oxygen were equivalent to the normals group at 21% oxygen (room air). The findings suggest that the muscle weakness observed in CRF patients is due to an impaired oxygen delivery system, probably as a result of degeneration in the capillary network. We are currently performing morphometry studies on biopsied samples from these subjects to corroborate these findings.