Extended exposure to microgravity (μG) is known to reduce strength in weight-bearing muscles and was also reported to reduce respiratory muscle strength. Short- duration exposure to μG reduces vital capacity (VC), a surrogate measure for respiratory muscle strength, for the first few days, with little change in O2 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 μG, and multiple times postflight. VC in μG 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 μG, but there were no changes postflight. Maximum respiratory pressures in μG were generally intermediate to those standing and supine in 1G, and importantly they showed no decrease with time spent in μG. O2 uptake and CO2 production were reduced (∼12%) in extended μG, but inhomogeneity in the lung was not different compared with short-duration exposure to μG. The results show that VC is essentially unchanged and respiratory muscle strength is maintained during extended exposure to μG, and metabolic rate is reduced.