An investigation was made into the effects of physical exercise upon heart glycogen change in rats exposed to decreased barometric pressure in hypobaric chamber simulating the effects of 3,000 m and 5,000 m altitude. Blood and cardiac tissue samples were examined after 1 h and 5 h of treadmill running at sea level and at 3,000 m, and after 1 h at 5,000 m. At sea level, cardiac glycogen level showed a classic biphasic evolution which was not affected by running. At 3,000 m, 1 h of running promoted an initial increase of 16% from control values, while a secondary decrease of 15% was measured after 5 h of running. Running for 1 h at 5,000 m induced a total depletion in cardiac glycogen level, the latter being depressed by 90% from control values. Free fatty acid (FFA) plasma level was increased by physical exercise at all barometric pressures, but the response was gradually enhanced by hypoxia. These data indicate that heart glycogen utilization during prolonged physical exercise is stimulated by acute altitude exposure, which suppresses the sparing effect observed at sea level upon dependence of enhanced FFA availability. The great differences in cardiac glycogen utilization support the views that enhanced glycogenolysis during hypoxia is promoted by different parameters, thus affecting various pathways. The slight decrease at 3,000 m suggests a moderate increase in anaerobic metabolism while the exhaustion observed after 1 h of running at 5,000 m indicates a decrease in cellular respiration response and enhanced heart anaerobic metabolism.