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The causes of exercise-induced hypoxemia (EIH) remain unclear. We studied the mechanisms of EIH in highly trained cyclists. Five subjects had no significant change from resting arterial(; 92.1 ± 2.6 Torr) during maximal exercise (C), and seven subjects (E) had a >10-Torr reduction in (81.7 ± 4.5 Torr). Later, they were studied at rest and during various exercise intensities by using the multiple inert gas elimination technique in normoxia and hypoxia (13.2% O₂). During normoxia at 90% peak O₂ consumption, was lower in E compared with C (87 ± 4 vs. 97 ± 6 Torr, P < 0.001) and alveolar-to-arterial O₂tension difference (a-) was greater (33 ± 4 vs. 23 ± 1 Torr,P < 0.001). Diffusion limitation accounted for 23 (E) and 13 Torr (C) of thea-(P < 0.01). There were no significant differences between groups in arterial() or ventilation-perfusion (V˙a/Q˙) inequality as measured by the log SD of the …