Purpose: This study examined the effects of gender on graded exercise stress test (GXT) response in moderate-altitude (MA)-acclimatized cyclists during sea-level (SL) simulation. It was hypothesized that alterations in arterial saturation would relate to changes in (V) over dot O-2peak. Methods: Twenty competitive cyclists (12 males, 8 females) who were residents of MA locations underwent two randomized bicycle GXTs: one under local normoxic hypobaria, and the other under simulated SL conditions. Results: Under the SL condition, the cyclists demonstrated a significant increase (2-3%) in absolute and relative (V) over dot O-2peak, improved (4%) economy at lactate threshold (LT), and time-adjusted peak power (7%); the range of improvement between individuals varied from -6% to +25%. Simulated SL also resulted in a greater arterial saturation (SaO2) at rest and (V) over dot O-2peak, and significantly less desaturation (4 vs 8%) from rest to (V) over dot O-2peak. The individual variability in the change (Delta) in (V) over dot O-2peak was not significantly correlated to SL SaO2 or any other SaO2 variable analyzed, regardless of whether we examined each gender individually or combined. Significant correlations were found between Delta-peak power and Delta-economy as well as Delta-(V) over dot O-2peak and Delta-GXT time. These correlations as well as degree of improvement varied by gender. Conclusions: These data suggest that chronic residence at MA may attenuate the occurrence of exercise-induced arterial hypoxemia and eliminate the relationship between SaO2 and Delta-(V) over dot O-2peak that has been reported among SL residents acutely exposed to altitude. Additionally, the improvements that occur in predictors of aerobic performance when MA residents are exposed acutely to SL conditions have a large degree of individual variability, and the mechanism(s) for improvement may vary by gender.