Pulmonary hemodynamics and gas exchange were studied in four physicians during 72 hr acclimatization to 12,470 ft. Pulmonary catheters were left in three subjects for 72 hr. Resting mean pulmonary arterial pressure (PAP) rose progressively during the first 24 hr from 10.3 +/-1.0 to 21.1 +/-4.0 torr and remained at this level. During this same 24 hr period cardiac output increased from 7.1 +/-1.4 to 8.4 +/-2.0 liters/min and total pulmonary resistance rose from 122 +/-16 to 209 +/-40 dynes.sec/cm(-5). Excercise at 60 w after 24 hr of hypoxia increased PAP to 28.8 +/-5.1 torr and decreased total pulmonary resistance to 155 +/-25. Shunt fractions were 11 +/-3.8% after 24 hr at altitude and fell to 7 +/-0% after 72 hr. Alveolar to arterial O(2) difference (P(A-a)(O2)) breathing oxygen fell from 116 +/-10.8 to 92 +/-33.3 torr during the same period of acclimatization, whereas dead space to tidal volume ratio (V(D)/V(T)) rose from 33 +/-4.0% to 40 +/-5.3% and P(A-a)(O2) breathing ambient air rose from 8 +/-2.6 to 11 +/-3.0 torr. Inspiratory static lung compliance decreased significantly from a control of 176 +/-8 to 141 +/-8 ml/cm H(2)O after 72 hr of hypoxia. After 4-7 days at altitude, further deterioration in gas exchange was observed after a 5 mile, 1800 ft climb to the summit (14,255 ft) and return. P(A-a)(O2) on air rose from 2.5 +/-2.1 just before starting, to 16.3 +/-2.8 at the summit (rested), and was still 9.0 +/-2.2 several hours after returning. The O(2)-breathing values paralleled these, whereas dead space appeared to fall. We speculate that the hypoxic pulmonary hypertension which develops over 24 hr in some way may be responsible for a reduction of compliance and deterioration in oxygen exchange efficiency, possibly representing a sub-clinical form of pulmonary edema of high altitude. The increased alveolar to arterial O(2) difference induced by hypoxic exercise persists for several hours of hypoxic rest.