Recent evidence suggests that heavy exercise may lower the percentage of O2 bound to hemoglobin (%SaO2) by greater than or equal to 5% below resting values in some highly trained endurance athletes. We tested the hypothesis that pulmonary gas exchange limitations may restrict VO2max in highly trained athletes who exhibit exercise-induced hypoxemia. Twenty healthy male volunteers were divided into two groups according to their physical fitness status and the demonstration of exercise-induced reductions in %SaO2 less than or equal to 92%: 1) trained (T), mean VO2max = 56.5 ml.kg-1.min-1 (n = 13) and 2) highly trained (HT) with maximal exercise %SaO2 less than or equal to 92%, mean VO2max = 70.1 ml.kg-1.min-1 (n = 7). Subjects performed two incremental cycle ergometer exercise tests to determine VO2max at sea level under normoxic (21% O2) and mild hyperoxic conditions (26% O2). Mean %SaO2 during maximal exercise was significantly higher (P less than 0.05) during hyperoxia compared with normoxia in both the T group (94.1 vs. 96.1%) and the HT group (90.6 vs. 95.9%). Mean VO2max was significantly elevated (P less than 0.05) during hyperoxia compared with normoxia in the HT group (74.7 vs. 70.1 ml.kg-1.min-1). In contrast, in the T group, no mean difference (P less than 0.05) existed between treatments in VO2max (56.5 vs. 57.1 ml.kg-1.min-1). These data suggest that pulmonary gas exchange may contribute significantly to the limitation of VO2max in highly trained athletes who exhibit exercise-induced reductions in %SaO2 at sea level.(ABSTRACT TRUNCATED AT 250 WORDS)