Maximal aerobic power at high altitude (<4000 m) does not increase with altitude acclimatization. In order to investigate the isolated effects of increased arterial oxygen content (CaO2) on maximal oxygen uptake (VO2max) in hypoxia, we studied 10 subjects during exercise in acute exposure to 12.6% O2 before and after novel erythropoiesis stimulating protein (NESP) induced increases in CaO2. Over a period of 1 month, weekly NESP treatment increased resting hemoglobin (Hb) from 13.8±0.9 to 16.2±0.5 g/dL, hematocrit from 42.1±0.6% to 49.0±1.5%, and CaO2 from 189.7±3.0 to 218.6±5.7 mL/L. At maximal exercise CaO2 was increased from 172.3±3.7 to 191.5±3.8 mL/L with NESP treatment, and although maximal heart rate was similar in both conditions (178.4±2.6 and 180.9±2.5 b.p.m.) VO2max remained unaltered, the values being 3.12±2.0 and 3.12±2.0, before and after NESP treatment, respectively. NESP-injections in human subjects causes Hb and accordingly CaO2 to increase both in normoxia and hypoxia. Despite increases in CaO2 at maximal exercise in hypoxia VO2max is not increased.