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Sheep that breathe pure oxygen via a tracheostomy develop progressive respiratory failure and die within four days. The characteristic terminal findings include an increased water content of the lung, a decrease in lung compliance, and severe hypercarbia.To sequentially assess alterations of lung transvascular fluid dynamics during prolonged oxygen breathing the authors measured lung lymph flow (Q lymph), protein transport (Q protein), and pulmonary vascular pressures in five sheep with chronic lung lymph fistulas. No significant changes of lung transvascular fluid dynamics occurred during the first 60 hours of oxygen breathing, although an increasing trend of Q lymph and Q protein was demonstrable. However, after 72 hours of oxygen breathing, Q lymph, Q protein, and extravascular lung water had increased significantly without any change of pulmonary vascular pressures. The authors conclude that the toxic effects of oxygen on the lungs of sheep include a delayed but marked increase of pulmonary microvascular permeability to protein and fluid.