Several products of the activated complement system are known to modulate endothelial cell function in vitro. It has been shown that the membrane attack complex (MAC) (C5b-C9) can enhance tumor necrosis factor alpha (TNF-)-induced expression of P- and E-selectin and intercellular adhesion molecule type 1 in cell cultures of human umbilical vein endothelial cells. In the present study the potential role of this synegism for lung injury during endotoxin-mediated septic shock in vivo was examined using a model of C6-deficient PVG (C) (RT1^C) rats and the congenic PVG (C+) (RT1^C) strain. Following administration of a high (5 mg/kg) or low (0.5 mg/kg) dose of lipopolysaccharide (LPS) (Escherichia coli O55:B5), we determined the expression of cytokines, chemokines, and adhesion molecules as well as the recruitment of leukocytes in the lung. Challenge with intraperitoneal i.p. injections of LPS resulted in a strong induction of TNF-, interleukin-1/, cytokine-induced neutrophil chemoattractant, interferon-inducible protein 10, macrophage inflammatory proteins 1 and 2, macrophage chemotactic protein 1, and P-selectin. However, there were no significant differences between PVG (C) and PVG (C+) rats. Immunoperoxidase staining showed a similar increase of lung infiltration by CD11b/c⁺ leukocytes in both rat strains. We therefore conclude that the described synergism between TNF- and the MAC of the complement system on the induction of endothelial adhesion molecules is dispensable for inflammatory processes during endotoxin-mediated septic shock in vivo.