Hypoxic preconditioning prevents cerebrovascular/cardiovascular disorders by increasing resistance to acute ischemic stress, but severe hypoxic exposure disturbs vascular hemodynamics. This study compared how various exercise regimens with/without hypoxia affect hemodynamics and oxygenation in cardiac, muscle, and cerebral tissues during severe hypoxic exposure. Sixty sedentary males were randomly divided into five groups. Each group (n = 12) received one of five interventions: 1) normoxic (21% O2) resting control, 2) hypoxic (15% O2) resting control, 3) normoxic exercise (50% maximum work rate under 21% O2; N-E group), 4) hypoxic-relative exercise (50% maximal heart rate reserve under 15% O2; H-RE group), or 5) hypoxicabsolute exercise (50% maximum work rate under 15% O2; H-AE group) for 30 min/day, 5 days/wk, for 4 wk. A recently developed noninvasive bioreactance device was used to measure cardiac hemodynamics, and near-infrared spectroscopy was used to assess perfusion and oxygenation in the vastus lateralis (VL)/gastrocnemius (GN) muscles and frontal cerebral lobe (FC). Our results demonstrated that the H-AE group had a larger improvement in aerobic capacity compared with the N-E group. Both H-RE and H-AE ameliorated the suppression of cardiac stroke volume and the GN hyperemic response (Atotal Hb/min) and reoxygenation rate by acute 12% O2 exposure. Simultaneously, the two hypoxic interventions enhanced perfusion (Atotal Hb) and O2 extraction [AdeoxyHb] of the VL muscle during the 12% O 2 exercise. Although acute 12% O2 exercise decreased oxygenation ($Δ$O2Hb) of the FC, none of the 4-wk interventions influenced the cerebral perfusion, and oxygenation during normoxic/ hypoxic exercise tests. Therefore, we conclude that moderate hypoxic exercise training improves cardiopulmonary fitness and increases resistance to disturbance of cardiac hemodynamics by severe hypoxia, concurrence with enhancing O2 delivery/utilization in skeletal muscles but not cerebral tissues. Copyright © 2010 the American Physiological Society.