Inhalation of toxic dust during planetary space missions may cause airway inflammation, which can be monitored with exhaled nitric oxide (NO). Gravity will differ from earth, and we hypothesized that gravity changes would influence exhaled NO by altering lung diffusing capacity and alveolar uptake of NO. Five subjects were studied during microgravity aboard the International Space Station, and 10 subjects were studied during hypergravity in a human centrifuge. Exhaled NO concentrations were measured during flows of 50 (all gravity conditions), 100, 200, and 500 ml/s (hypergravity). During microgravity, exhaled NO fell from a ground control value of 12.3 +/- 4.7 parts/billion (mean +/- SD) to 6.6 +/- 4.4 parts/billion (P = 0.016). In the centrifuge experiments and at the same flow, exhaled NO values were 16.0 +/- 4.3, 19.5 +/- 5.1, and 18.6 +/- 4.7 parts/billion at one, two, and three times normal gravity, where exhaled NO in hypergravity was significantly elevated compared with normal gravity (P <or= 0.011 for all flows). Estimated alveolar NO was 2.3 +/- 1.1 parts/billion in normal gravity and increased significantly to 3.9 +/- 1.4 and 3.8 +/- 0.8 parts/billion at two and three times normal gravity (P < 0.002). The findings of decreased exhaled NO in microgravity and increased exhaled and estimated alveolar NO values in hypergravity suggest that gravity-induced changes in alveolar-to-lung capillary gas transfer modify exhaled NO.