Introduction: The activation of leukocytes by bacterial cell wall lipopolysaccharide (LPS) contributes to the pathogenesis of septic shock. LPS is known to interact with several cell-surface proteins, including CD14 when presented as a complex with serum LPS-binding protein (LBP). However, the identity of the receptor responsible for LPS signalling and leukocyte activation is unknown. Interestingly, mice deficient in cell surface L-selectin were dramatically resistant to the lethal effects of high doses of LPS in a model of septic shock (Tedder et al., (1995) J Expt Med. 181, 2259). Recently, we reported that L-selectin binds to cardiolipin and other charged phospholipids at a site distinct from the carbohydrate binding site (Malhotra et al., (1996) Biochemical J. 314, 297). Structural similarities between charged phospholipids and the lipid-A moiety of LPS prompted us to investigate interactions between L-selectin and LPS.Materials and Methods: LPS was immobilised on microtitre plate wells and binding of recombinant L-selectin to bound LPS was investigated. Neutrophils were isolated from freshly drawn human blood and effect of LPS or Fucoidan on superoxide production and TNF-α was investigated.Results: Data will be presented to show that L-selectin is a neutrophil surface receptor for LPS and lipotechoic acids. The binding of LPS to L-selectin is independent of serum and Ca 2 + , and is blocked by antibodies to L-selectin and fucoidan. Furthermore, the interaction of LPS with cell surface L-selectin results in superoxide production and secretion of TNF-α, indicating that L-selectin can mediate both binding and activation of human neutrophils.Conclusion: These findings suggest a possible role of L-selectin in bacteria-induced septic shock.