The purpose of this study was to determine the effects of inspiratory muscle training (IMT) on exercise in hypoxia (H) and normoxia (N). A 4-week IMT program was implemented with 12 healthy subjects using an inspiratory muscle trainer set at either 15% (C; n=5) or 50% (IMT; n=7) maximal inspiratory mouth pressure (PImax). Two treadmill tests (85% VO2max) to exhaustion and measures of diaphragm thickness (Tdi) and function were completed before and after training in H and N. Significant increases of 8-12% and 24.5+/-3.1% in Tdi and PImax, respectively, were seen in the IMT group. Time to exhaustion remained unchanged in all conditions. Inspiratory muscle fatigue (downward arrowPImax) following exercise was reduced approximately 10% (P<0.05) in IMT after both N and H. During H, IMT reduced (P<0.05) VO2 by 8-12%, cardiac output by 14+/-2%, ventilation by 25+/-3%; and increased arterial oxygen saturation by 4+/-1% and lung diffusing capacity by 22+/-3%. Ratings of perceived exertion and dyspnea were also significantly reduced. These data suggest that IMT significantly improves structural and functional physiologic measures in hypoxic exercise.