Some highly trained endurance athletes develop an exercise-induced hypoxemia (EIH) at least partially due to a hemodynamic factor with a potential stress failure on pulmonary capillaries. Atrial natriuretic factor (ANF) is a pulmonary vasodilatator and its release during exercise could be reduced with endurance training. We hypothesized that athletes exhibiting EIH, who have a greater training volume than non-EIH athletes, have a reduced ANF release during exercise explaining the pathophysiology of EIH. Ten highly trained EIH-athletes (HT-EIH), ten without EIH (HT-nEIH), and nine untrained (UT) males performed incremental exercise to exhaustion. No between group differences occurred in resting ANF plasma levels. In contrast to HT-nEIH and UT (p < 0.05), HT-EIH showed a smaller increase in ANF concentration between rest and maximal exercise (HT-EIH: 8.12 +/- 0.69 vs. 14.1 +/- 1.86 pmol x l (-1); HT-nEIH: 10.46 +/- 1 vs. 18.7 +/- 1.8 pmol x l (-1); UT: 6.23 +/- 0.95 vs. 20.38 +/- 2.79 pmol x l (-1)). During the recovery, ANF levels decreased significantly in HT-nEIH and UT groups (p < 0.05). Electrolyte values increased in all groups during exercise but were higher in both trained groups. In conclusion, this study suggested that ANF response to exercise may be important for exercise-induced hypoxemia.