Hales, Charles A., T. H. Elsasser, Peter Ocampo, and Olga Efimova. TNF-α in smoke inhalation lung injury. J. Appl. Physiol. 82(5): 1433–1437, 1997.—Adult respiratory distress syndrome is a major cause of morbidity in fire victims. Tumor necrosis factor-α (TNF-α) is edematogenic and has been associated with the etiology of other forms of adult respiratory distress syndrome. In the sheep lymph fistula model, we measured TNF-α after 48 ( n = 7) or 128 ( n = 3) breaths of cotton smoke and compared this with sham controls ( n = 5) or controls in which left atrial pressure was elevated to 20 mmHg ( n = 5) to increase lymph flow in the absence of inflammation. Smoke induced a rise in lymph flow and pulmonary arterial pressure with either no fall in lymph-to-plasma protein ratio (128 breaths) or a modest fall in lymph-to-plasma protein ratio (48 breaths), consistent with a change in microvascular permeability as well as a rise in microvascular pressure. Lymph concentration of TNF-α fell in both groups, although lymph flux (concentration × flow) transiently rose in both. In neither case did TNF-α flux exceed that induced by left atrial pressure elevation. TNF-α was detectable in only one out of five sheep in alveolar lavage. Thus, by utilizing a sensitive and specific radioimmunoassay, we were unable to demonstrate a role for TNF-α in smoke-induced microvascular lung injury in sheep.