Reports of VO2 response differences between normoxia and hypoxia during incremental exercise do not agree. In this study VO2 and VE were obtained from 15-s averages at identical work rates during continuous incremental cycle exercise in 8 subjects under ambient pressure (633 mmHg ≈1,600 m) and during duplicate tests in acute hypobaric hypoxia (455 mmHg ≈4,350 m), ranging from 49 to 100% of VO2 peak in hypoxia and 42–87% of VO2 peak in normoxia. The average VO2 was 96 mL/min (619 mL) lower at 455 mmHg (n.s. P = 0.15) during ramp exercises. Individual response points were better described by polynomial than linear equations (mL/min/W). The VE was greater in hypoxia, with marked individual variation in the differences which correlated significantly and directly with the VO2 difference between 455 mmHg and 633 mmHg (P = 0.002), likely related to work of breathing (Wb). The greater VE at 455 mmHg resulted from a greater breathing frequency. When a subject's hypoxic ventilatory response is high, the extra work of breathing reduces mechanical efficiency (E). Mean ∆E calculated from individual linear slopes was 27.7 and 30.3% at 633 and 455 mmHg, respectively (n.s.). Gross efficiency (GE) calculated from mean VO2 and work rate and correcting for Wb from a VE–VO2 relationship reported previously, gave corresponding values of 20.6 and 21.8 (P = 0.05). Individual variation in VE among individuals overshadows average trends, as also apparent from other reports comparing hypoxia and normoxia during progressive exercise and must be considered in such studies.