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Purpose: Bolus intravenous administration of 0.9% saline has been associated with the development of pulmonary edema, and increased mortality. An animal model has previously demonstrated that rapid intravenous administration of 0.9% saline was associated with non-hydrostatic lung injury with increased lung lavage protein. We hypothesized that this non-hydrostatic effect would also occur in human volunteers. Methods: In a randomized, cross-over study of 14 healthy male subjects, the lung lavage protein concentration and cardiorespiratory effects of an intervention with rapid intravenous administration of 30 mL/kg of 0.9% saline were compared with sham intervention. Bronchoalveolar lavage (BAL) was performed after fluid administration. Doppler echocardiography, lung ultrasound, pulmonary function tests, and blood sampling were performed before and after each intervention. Results: The BAL total protein concentration was greater after 0.9% saline administration than with sham (196.1 µg/mL (SD 87.6) versus 129.8 µg/mL (SD 55.4), respectively (p = 0.020). Plasma angiopoietin-2 concentration was also increased to 2.26 ng/mL (SD 0.87) after 0.9% saline administration compared with sham 1.53 ng/mL (SD 0.69) (p < 0.001). There were small increases in stroke volume (from 58 mL (IQR 51–74) to 66 mL (IQR 58–74), p = 0.045) and Doppler echocardiography left ventricle E/e' ratio (from 5.0 (IQR 4.5–6.0) to 5.7 (IQR 5.3–6.3), p = 0.007), but no changes to right ventricular function. Conclusion: Rapid intravenous administration of 0.9% saline leads to interstitial permeability pulmonary edema in healthy human volunteers. Further research is now warranted to understand these effects in critically ill patients. [ABSTRACT FROM AUTHOR]