The basis for surfactant accumulation after silica exposure is not known. As a result of an association between elevations in extracellular surfactant and oxidant exposures, the authors tested the hydpothesis that (1) surfactant=enriched material can function as an in vitro target for oxidants catalyzed by Fe (3+) complexed to the surface of silica, and (2) in vivo alveolar accumulation of surfactant after exposure of the lower respiratory tract to silica is associated with the concentration of Fe (3+) complexed to the dust surface. Surfactant-enriched material was incubated in both chemical and cellular systems with either Gey's balanced salt solution, acid-washed silica, deferoxamine-treated silica, wetted silica, or iron-loaded silica. The absorbance of oxidized products was associated with concentrations of complexed iron on the surface of the silica dust. Rats (n = 10/group) were intratracheally instilled with either normal saline, 6.0 mg acid-washed silica, 6.0 mg deferoxamine-treated silica, 6.0 mg wetted silica, or 6.0 mg iron-loaded silica, Ninety-six hours after tracheal instillation, silica singificantly increased extracellular surfactant as reflected by lipid phosphorous in the total lavage fluid. Lipid accumulation was associated with concentrations of surfact complexed iron on the surface of the silica.