This study was conducted to investigate whether the changes in the pulmonary diffusing capacity found in individuals with acute mountain sickness (AMS) reflect the early stage of high-altitude pulmonary edema (HAPE). We measured the pulmonary diffusion capacity for carbon monoxide (DCO) by the single-breath method, arterialized capillary blood gas, and spirometry in a group of 32 healthy subjects (24 men, eight women) at an altitude of 2,260 m and after ascent to 4,700 m. Twelve subjects (10 men, two women) had symptoms of AMS (AMS group) by the second day after arrival at 4,700 m, but none had clinical signs of pulmonary or cerebral edema. In the non-AMS group, almost all subjects exhibited an increase in DCO at 2,260 to 4,700 m (ΔDCO, 10.7±1.25 mL/min/mm Hg), while the degree of increase in DCO in the AMS group (n=12) was significantly lower (ΔDCO, 1.26±1.74 mL/min/mm Hg) than that of the non-AMS group (p<0.01). In four of the 12 subjects with AMS who had a high AMS score, DCO decreased from 38.4±4.5 to 33.2±5.3 mL/min/mm Hg (ΔDCO, −5.84±1.1 mL/min/mm Hg). The AMS group showed significantly lower vital capacity, forced expiratory flow during the middle half of FVC, Pa02, and a greater alveolar-arterial oxygen pressure difference at 4,700 m compared with the non-AMS group. DCO showed a significant negative correlation with AMS score (r=−0.885) and a positive correlation with PaO2 (r=0.757) at 4,700 m. These results suggest that the decreased pulmonary diffusing capacity in subjects with AMS reflects the presence of pulmonary gas exchange abnormality, which is probably due to subclinical interstitial edema of the lung.