The effects of hypoxemia on inspiratory muscle fatigue were assessed in 4 normal subjects. They breathed to exhaustion through high inspiratory resistances producing an inspiratory mouth pressure (Pm) of about 80% of maximal mouth pressure. The endurance time (tlim) during hypoxia (13% O2) was found to be shorter than that while breathing room air at equal inspiratory mouth pressures. Endurance time during hypoxia was also compared with that while breathing room air at equal rates of energy consumption (C), assuming that C is proportional to: Formula: (See Text). At these equal rates, endurance time during hypoxia still remained shorter than that during normoxia. Fatigue was also assessed by measuring the electromyographic power spectrum of the diaphragm and the parasternal intercostals. The power spectrum shifted towards low frequencies during fatigue and a greater rate of shift was observed under hypoxic conditions. The rate of lactate production during hypoxemia was greater than that during normoxia; however, blood lactate concentrations at the end of the tests were similar under both conditions. It was concluded that respiratory muscles, working against high inspiratory resistances, fall as pressure generators sooner during low oxygen breathing. The effect of low oxygen breathing on inspiratory muscle fatigue resulted in a shorter endurance time, a faster rate in the shift of the electromyographic power spectrum, and a greater rate of increase in blood lactate concentrations.