We measured pulmonary diffusing capacity (DL), diffusing capacity per unit lung volume, pulmonary capillary blood volume (Vc), membrane diffusing capacity (Dm), pulmonary capillary blood flow or cardiac output (Qc), and cardiac stroke volume (SV) in four subjects exposed to 9 days of microgravity (weightlessness, 0 G). The same subjects were studied standing and supine numerous times preflight and in the week immediately after return from space. DL in microgravity was elevated (28%) compared with preflight standing values and was higher than preflight supine because of the elevation of both Vc (28%) and Dm (27%). The elevation in Vc was comparable to that measured supine in 1 G, but the increase in Dm was in sharp contrast to the supine value (which was unchanged). We postulate that, in 0 G, pulmonary capillary blood is evenly distributed throughout the lung, providing for uniform capillary filling, leading to an increase in the surface area available for diffusion. By contrast, in the supine 1-G state, the capillaries are less evenly filled, and although a similar increase in blood volume is observed, the corresponding increase in surface area does not occur. DL and its subdivisions showed no adaptive changes from the first measurement 24 h after the start of 0 G to 8 days later. Similarly, there were no trends in the postflight data, suggesting that the principal mechanism of these changes was gravitational. The increase in Dm suggests that subclinical pulmonary edema did not result from exposure to 0 G. Qc was modestly increased (18%) inflight and decreased (9%) post-flight compared with preflight standing. Compared with preflight standing, SV was increased 46% inflight and decreased 14% in the 1st wk postflight. There were temporal changes in Qc and SV during 0 G, with the highest values recorded at the first measurement, 24 h into the flight. The lowest values of Qc and SV occurred on the day of return.