Romer LM, Polkey MI. Exercise-induced respiratory muscle fatigue: implications for performance. J Appl Physiol 104: 879 -888, 2008. First published December 20, 2007 doi:10.1152/japplphysiol.01157.2007.-It is commonly held that the respiratory system has ample capacity relative to the demand for maximal O 2 and CO2 transport in healthy humans exercising near sea level. However, this situation may not apply during heavy-intensity, sustained exercise where exercise may encroach on the capacity of the respiratory system. Nerve stimulation techniques have provided objective evidence that the diaphragm and abdominal muscles are susceptible to fatigue with heavy, sustained exercise. The fatigue appears to be due to elevated levels of respiratory muscle work combined with an increased competition for blood flow with limb locomotor muscles. When respiratory muscles are prefatigued using voluntary respiratory maneuvers, time to exhaustion during subsequent exercise is decreased. Partially unloading the respiratory muscles during heavy exercise using low-density gas mixtures or mechanical ventilation can prevent exercise-induced diaphragm fatigue and increase exercise time to exhaustion. Collectively, these findings suggest that respiratory muscle fatigue may be involved in limiting exercise tolerance or that other factors, including alterations in the sensation of dyspnea or mechanical load, may be important. The major consequence of respiratory muscle fatigue is an increased sympathetic vasoconstrictor outflow to working skeletal muscle through a respiratory muscle metaboreflex, thereby reducing limb blood flow and increasing the severity of exerciseinduced locomotor muscle fatigue. An increase in limb locomotor muscle fatigue may play a pivotal role in determining exercise tolerance through a direct effect on muscle force output and a feedback effect on effort perception, causing reduced motor output to the working limb muscles. respiratory muscles; exercise; diaphragm; abdominals; magnetic stimulation; metaboreflex THE PURPOSE OF THIS MINIREVIEW is to address the question of whether the respiratory demands of exercise contribute significantly toward exercise limitation, either directly through limitations of the respiratory muscle pump or indirectly through effects on limb blood flow and locomotor muscle fatigue. We describe the mechanical and metabolic costs of meeting the ventilatory requirements of exercise. We then ask whether the respiratory muscles fatigue with exercise, what factors contribute to any such fatigue, and what the implications of these factors are for exercise tolerance. Finally, we deal with the potential mechanisms by which respiratory muscle fatigue could compromise exercise tolerance and whether it is possible to overcome this potential respiratory limitation. Our review focuses on the healthy young adult exercising near sea level. However, we also consider special circumstances that determine the balance between metabolic demand and respiratory system capacity in the highly trained endurance ...