The question of respiratory factors limiting exercise has been examined in terms of possible limitations arising from the function of gas exchange, the respiratory mechanics, the energetics of the respiratory muscles, or the development of respiratory muscle fatigue. Exercise capacity is curtailed in the presence of marked hypoxia, and this is readily observed in patients with chronic airflow limitation and interstitial lung disease and in some athletes at high intensities of exercise. In patients with interstitial lung disease, gas exchange abnormality--partly the result of diffusion disequilibrium for oxygen transfer--occurs during exercise despite abnormally high ventilations. In contrast, in certain athletes arterial hypoxemia has been documented during heavy exercise, apparently as a result of relative hypoventilation. During strenuous exercise the maximum expiratory flow volume curves are attained both by patients with chronic airflow limitation and by normal subjects, in particular when they breathe dense gas, so that a mechanical constraint is imposed on further increases in ventilation. Similarly, the force velocity characteristics of the inspiratory muscles may also impose a constraint to further increases in inspiratory flows that affects the ability to increase ventilation. In addition, the oxygen cost of maintaining high ventilations is large. Analysis of results from blood flow experiments reveal a substantial increase in blood flow to the respiratory muscles during exercise, with the result that oxygen supply to the rest of the body may be lessened. Alternatively, high exercise ventilations may not be sustained indefinitely owing to the development of respiratory muscle fatigue that results in hypoventilation and reduced arterial oxygen tension.