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We tested the hypothesis that prolonged administration of moderate doses of recombinant human erythropoietin (r-HuEPO) accelerates the initial rate of rise in pulmonary O2 uptake (VO2) in response to submaximal exercise and increases the maximal rate of O2 uptake (VO2,max). Sixteen endurance-trained athletes were divided into two groups: r-HuEPO- (n=9) or placebo-treated (n=7). r-HuEPO or placebo (saline) injections were given s.c. 3 times a week for 4 weeks. Exercise testing, before and after the 4 weeks, comprised incremental maximal tests and several transitions from rest to 10-min cycling exercise at 65% VO2,max. VO2 was measured breath-by-breath during all tests. In the r-HuEPO group, resting haemoglobin concentration (+9.6%) and haematocrit (+8.3%), as well as VO2,max (+7.0%) and power output (+7.2%) increased significantly (P<0.05) after the 4 weeks, whereas no change was observed in the control group. The time constant of the primary VO2 response was significantly faster (+18%) after the 4 weeks r-HuEPO treatment than before (mean±SD; 29.3±4.5 vs. 35.7±7.4 s, respectively, P<0.05) but was unaffected in the placebo group (34.5±7.3 vs. 33.4±7.9 s). Collectively, our findings suggest that r-HuEPO contributes both to an acceleration of the dynamic response of VO2 to submaximal exercise and to an increase in maximal exercise capacity. [ABSTRACT FROM AUTHOR]