In the healthy, untrained young adult a case is made for a respiratory system- airways, pulmonary vasculature, lung parenchyma, respiratory muscles and neural ventilatory control system - which is near ideally designed to ensure a highly efficient, homeostatic response to exercise of varying intensities and durations. Our aim was then to consider circumstances in which the intra/extra-thoracic airways, pulmonary vasculature, respiratory muscles and/or blood:gas distribution are underbuilt or inadequately regulated relative to the demands imposed by the cardiovascular system. In these instances, the respiratory system presents a significant limitation to O transport and contributes to the occurrence of locomotor muscle fatigue, inhibition of central locomotor output and exercise performance. Most prominent in these examples of an "underbuilt" respiratory system are highly trained endurance athletes, with additional influences of sex, aging, hypoxic environments and the highly inbred equine. We summarize by evaluating the relative influences of these respiratory system limitations on exercise performance, their impact on pathophysiology and provide recommendations for future investigation.2