Endotoxin, or lipopolysaccharide (LPS), is the major gram-negative bacterial cell wall toxin that triggers septic shock (1). Gram-negative endotoxin is shed from the membrane of rapidly proliferating bacteria, and enhanced release into the blood is associated with antibiotic use (2). Endotoxin is also translocated through the gut after periods of hypotension often associated with cardiopulmonary bypass or hypovolemic shock (3). LPS has been demonstrated to enter the systemic circulation from the lung in experimental animal studies and human clinical investigations. In the blood, LPS binds to a carrier protein, which acts as a chaperone to carry this molecule to CD14 receptors on immunocompetent cells to trigger pro-inflammatory cytokine synthesis (tumor necrosis factor). To date, the detection of LPS in blood or plasma has been largely dependent on variations of the limulus amebocyte lysate (LAL) assay, which utilizes the clotting enzyme cascade extracted from the primitive “white cell like” amebocyte cells of horseshoe crabs to detect LPS. The effectiveness of this assay in human blood and blood plasma has been controversial and problematic because of numerous interfering reactions and variations in between-lot and between-manufacturer reagent performance. We have developed a rapid, homogeneous assay for the detection of endotoxin activity (EA) in whole blood based on in vitro neutrophil activation (4). This novel type of assay uses the priming effects of complement opsonized immune complexes on the respiratory burst activity of neutrophils as an analytical platform. Hypochlorous acid generated by the concerted activity of membrane-bound NADPH oxidase and azurophil granule myeloperoxidase of the neutrophil produces luminol chemiluminescence. Although immune complexes formed by the interaction of antibody with antigen do not directly stimulate neutrophil respiratory bursts, they …