Purpose: We investigated the effects of recombinant human erythropoietin (rHuEPO) administration on exercise endurance, maximal aerobic performance, and total hemoglobin mass (tHb). We hypothesized that frequent, small intravenous injections of epoetin β would increase time trial performance, peak oxygen uptake (V̇O2peak), and tHb in both males and females. Methods: We included 48 healthy, recreational to trained males (n = 24, mean ± SD V̇O2peak = 55 ± 5 mL O2·kg−1⋅min−1) and females (n = 24; V̇O2peak of 46 ± 4 mL O2·kg−1⋅min−1) in a counterbalanced, double-blind, randomized, placebo-controlled study design stratified by sex. Time trial performance, V̇O2peak, and tHb were determined before and after intravenous injections of either rHuEPO (9 IU·kg bw−1 epoetin β) or saline (0.9% NaCl) three times weekly for 4 wk. Results: A time–treatment effect (P < 0.05) existed for time trial performance. Within the rHuEPO group, mean power output increased by 4.1% ± 4.2% (P < 0.001). Likewise, a time–treatment effect (P < 0.001) existed for V̇O2peak, where the rHuEPO group improved V̇O2peak and peak aerobic power by 4.2% ± 6.1% (P < 0.001) and 2.9% ± 4.0% (P < 0.01), respectively. A time–treatment effect (P < 0.001) existed for tHb, where the rHuEPO group increased tHb by 6.7% ± 3.4% (P < 0.001). A main effect of "sex" alone was also evident (P < 0.001), but no sex-specific interactions were found. No changes were observed in the placebo group for mean power output, V̇O2peak, peak aerobic power, or tHb. Conclusions: Microdoses with intravenous rHuEPO provide a sufficient erythropoietic stimuli to augment tHb and enhance aerobic-dominated performance in both trained males and females. [ABSTRACT FROM AUTHOR]