West. Vital capacity, respiratory muscle strength, and pulmonary gas exchange during long-duration exposure to microgravity. J Appl Physiol 101: 439-447, 2006. First published April 6, 2006; doi: 10.1152/japplphysiol. 01419.2005.-Extended exposure to microgravity (mu G) is known to reduce strength in weight-bearing muscles and was also reported to reduce respiratory muscle strength. Short-duration exposure to mu G reduces vital capacity (VC), a surrogate measure for respiratory muscle strength, for the first few days, with little change in O-2 uptake, ventilation, or end-tidal partial pressures. Accordingly we measured VC, maximum inspiratory and expiratory pressures, and indexes of pulmonary gas exchange in 10 normal subjects (9 men, 1 woman, 39-52 yr) who lived on the International Space Station for 130-196 days in a normoxic, normobaric atmosphere. Subjects were studied four times in the standing and supine postures preflight at sea level at 1 G, approximately monthly in mu G, and multiple times postflight. VC in mu G was essentially unchanged compared with preflight standing [5.28 +/- 0.08 liters (mean +/- SE), n = 187; 5.24 +/- 0.09, n = 117, respectively; P = 0.03] and considerably greater than that measured supine in 1G (4.96 +/- 0.10, n = 114, P < 0.001). There was a trend for VC to decrease after the first 2 mo of mu G, but there were no changes postflight. Maximum respiratory pressures in mu G were generally intermediate to those standing and supine in 1G, and importantly they showed no decrease with time spent in mu G. O-2 uptake and CO2 production were reduced (similar to 12%) in extended mu G, but inhomogeneity in the lung was not different compared with short-duration exposure to mu G. The results show that VC is essentially unchanged and respiratory muscle strength is maintained during extended exposure to mu G, and metabolic rate is reduced.