A native of the Peruvian Andes (4,250 m) was studied before and after isovolemic hemodilution of the hematocrit from 62 to 42%. O2 transport was studied with newly developed catheters in the radial and pulmonary arteries. These catheters allowed continuous measurement of arteriovenous O2 content and intermittent cardiac output by thermodilution. During exercise tests, breath-by-breath gas exchange measurements also allowed cardiac output to be calculated by the O2-Fick technique. A complex series of interrelated physiological changes occurred in response to hemodilution. These included increased ventilation, increased arterial and mixed venous PO2, increased cardiac output (both heart rate and stroke volume), and improved ventilation-flow match. The general improvement in symptoms that followed hemodilution correlated well with increased anaerobic threshold and mixed venous PO2 during exercise.