Exercise-induced intrapulmonary arteriovenous shunting, as detected by saline contrast echocardiography, has been demonstrated in healthy humans. We have previously suggested that increases in both pulmonary pressures and blood flow associated with exercise are responsible for opening these intrapulmonary arteriovenous pathways. In the present study, we hypothesized that, although cardiac output and pulmonary pressures would be higher in hypoxia, the potent pulmonary vasoconstrictor effect of hypoxia would actually attenuate exercise-induced intrapulmonary shunting. Using saline contrast echocardiography, we examined nine healthy men during incremental (65W + 30W/2min) cycle exercise to exhaustion in normoxia and hypoxia (FIO₂=0.12). Contrast injections were made into a peripheral vein at rest and during exercise and recovery (3-5 min post-exercise) with pulmonary gas exchange measured simultaneously. At rest, no subject demonstrated intrapulmonary shunting in normoxia (PaO₂= 98 ± 10 Torr), whereas, in hypoxia (PaO₂= 47 ± 5 Torr) intrapulmonary shunting developed in 3/9 subjects. During exercise, ~90% (8/9) of the subjects shunted during normoxia whereas all subjects shunted during hypoxia. Four of the nine subjects shunted at a lower workload in hypoxia. Furthermore, all subjects continued to shunt at 3 min and 5 subjects shunted at 5 min post exercise in hypoxia. Hypoxia has acute effects by inducing intrapulmonary arteriovenous shunt pathways at rest and during exercise and has long term effects by maintaining patency of these vessels during recovery. Whether oxygen tension specifically regulates these novel pathways or opens them indirectly via effects on the conventional pulmonary vasculature remains unclear.