This study was conducted to determine whether arterial desaturation would occur at submaximal workloads in highly trained endurance athletes and whether saturation is affected by the fraction of oxygen in inspired air (F(I)O2). Six highly trained endurance athletes (5 women and 1 man, aged 25+/-4 yr, VO2max 71.3+/-5.0 ml x kg(-1) x min(-1)) ran 4x4 min on a treadmill in normoxia (F(I)O2 0.209), hypoxia (F(I)O2 0.155) and hyperoxia (F(I)O2 0.293) in a randomized order. The running velocities corresponded to 50, 60, 70 and 80% of their normoxic maximal oxygen uptake (VO2max). In hypoxia, the arterial haemoglobin oxygen saturation percentage (SpO2%) was significantly lower than in hyperoxia and normoxia throughout the test, and the difference became more evident with increasing running intensity. In hyperoxia, the SpO2% was significantly higher than in normoxia at 70% running intensity as well as during recovery. The lowest values of SpO2% were 94.0+/-3.8% (P<0.05, compared with rest) in hyperoxia, 91.0+/-3.6% (P<0.001) in normoxia and 72.8+/-10.2% (P<0.001) in hypoxia. Although the SpO2% varied with the F(I)O2, the VO2 was very similar between the trials, but the blood lactate concentration was elevated in hypoxia and decreased in hyperoxia at the 70% and 80% workloads. In conclusion, elite endurance athletes may show an F(I)O2-dependent limitation for arterial O2 saturation even at submaximal running intensities. In hyperoxia and normoxia, the desaturation is partly transient, but in hypoxia the desaturation worsens parallel with the increase in exercise intensity.