Data from the Spacelab Life Sciences-1 (SLS-1) mission have shown sustained but moderate increase in pulmonary diffusing capacity (DL). Because of the occupational constraints of the mission, data were only obtained after 24 h of exposure to microgravity. Parabolic flights are often used to study some effects of microgravity, and we measured changes in DL occurring at the very onset of weightlessness. Measurements of DL, membrane diffusing capacity, and pulmonary capillary blood volume were made in 10 male subjects during the 20-s 0-G phases of parabolic flights performed by the "zero-G" Caravelle aircraft. Using the standardized single-breath technique, we measured DL for CO and nitric oxide simultaneously. We found significant increases in DL for CO (62%), in membrane diffusing capacity for CO (47%), in DL for nitric oxide (47%), and in pulmonary capillary blood volume (71%). We conclude that major changes in the alveolar membrane gas transfers and in the pulmonary capillary bed occur at the very onset of microgravity. Because these changes are much greater than those reported during sustained microgravity, the effects of rapid transition from hypergravity to microgravity during parabolic flights remain questionable.