Lipopolysaccharide (LPS) induction of TNF-alpha release is a central event in the pathophysiology of gram-negative bacterial septicaemia. Lung surfactant protein A (SP-A) mediates pathogen/host cell interactions. Binding of SP-A to Pseudomonas aeruginosa LPS and the effects of SP-A with LPS or whole bacteria on buffy coat cells were investigated. SP-A interacts with P. aeruginosa LPS in a concentration and calcium dependent manner, either through the lipid A portion of LPS or through another lectin/carbohydrate interaction. SP-A decreased TNF-alpha secretion induced by bacteria or LPS from buffy coat cells, in a concentration dependent manner.