Oleic acid (OA) causes reversible lung injury which resolves in 5-7 days. This injury is characterized by inflammatory cell infiltration, changes in surfactant phospholipids and derangements in pulmonary function which peaks at 4-24 h after injury and begins to resolve by 72 h without permanent damage to alveolar epithelium. Surfactant protein A (SP-A) has been shown to be involved in pulmonary defense during lung inflammation, and SP-A may also be a proinflammatory mediator. Our hypothesis is that OA causes a reversible change in SP-A production and/or release and that SP-A may be involved in the reversible injury that occurs after OA administration. Adult rats were treated with either saline or OA i.v. after which lung lavage was collected at 1, 4, 24, 72h and 120h. Lungs were also removed. Lavage samples were centrifuged, to remove debris and cells, and then concentrated 15-fold. Lungs were homogenized and protein content was measured. Equivalent amounts of lung lavage and lung homogenates were separated by SDS-PAGE. Immunoblots were processed using polyclonal anti-rat SP-A antibody, and SP-A bands were analyzed by densitometry. There was a decrease in SP-A protein levels in lavage at 1, 4, and 24 hours after OA injury. Levels returned to normal by 72 h after injury. In contrast there was an increase in SP-A protein levels in lung homogenates at 1, 4, 24 and 72 hours after OA injury. The peak response was a 2-fold increase over controls at 4-24 h. We conclude that OA injury inhibits release of SP-A during the acute injury phase which resolves as the injury heals. It is possible that OA directly inhibits secretion of SP-A by type II cells and Clara cells. Alternatively, OA may cause release of both proinflammatory and antiinflammatory cytokines which in turn affect SP-A release. We speculate that the decreased release of SP-A (with known inflammatory actions) into the alveolus may be involved in the reversibilty of the OA injury. Funded in part by NIH grant HL-49099 (MJK).