Human endurance, both at altitude and at sea level, depends upon the ability of the subject to transport oxygen from the atmosphere to the working tissues. Many physiological processes were involved in oxygen transport, including the oxygen cost of breathing, the ventilation of alveolar gas, diffusion in the lungs, blood transport, and diffusion within the tissues. At sea level, the blood transport term (effectively the product of haemoglobin level and maximum cardiac out) offers the major resistance to oxygen uptake. At moderate altitudes, such as Denver (5000 ft) and Mexico City (7350 ft), alveolar ventilation (measured under STPD conditions) is well maintained, and the normal shape of the oxygen dissociation curve increases the effective solubility of oxygen in the blood stream, partially compensating for the increasing resistance offered by the pulmonary diffusion/blood transport interaction. However, if unacclimatized men are exposed acutely to an altitude of 7350 ft, their maximum oxygen intake is decreased by at least 8-10%, and there is a corresponding loss of performance in endurance events. The average sedentary indi vidual notices nothing more than a little breathlessness at this altitude, probably because in sub-maximum exercise, compensation is readily achieved by an increase of ventilation (measured at body temperature and pressure) and pulse rate. With more prolonged residence at altitude, compensation is also affected by adjustment of buffering systems and an increase of haemoglobin level. The altitude of Mexico City is rather critical from the physiological standpoint; at higher altitudes, compensation is no longer possible by increase of ventilation and use of the normal oxygen dissociation characteristics of haemoglobin. The pulmonary diffusion/blood transport resistance becomes increasingly significant, arterial saturation falls, and there is a progressive loss of maximum oxygen intake. Above 10,000 ft, the problem is compounded by the danger that unaccustomed severe exertion may induce pulmonary oedema.