Supernatants of endotoxin-activated monocytes have been shown to stimulate human neutrophil adherence to rat liver sinusoidal endothelial cells 3-4-fold. Evidence will be presented that tumor necrosis factor (TNF) is responsible for this phenomenon: (a) in high-performance gel filtration of supernatants of lipopolysaccharide-activated monocytes, neutrophil adhesion-inducing activity coeluted with TNF activity measured in the L929 cell-lysing assay at 25-45 kDa; (b) anti-TNF antibody treatment of supernatants of activated macrophages abolished their adhesion-inducing activity; (c) human recombinant TNF alpha stimulated neutrophil adhesion to sinusoidal endothelial cells in a dose-dependent manner. In addition, polymyxine B sulfate, which was capable of neutralizing direct effects of lipopolysaccharide on neutrophil adhesion, could abolish neither the neutrophil-adhesion-inducing activity of the supernatants of endotoxin-activated monocytes nor the effect of human recombinant TNF itself. The neutrophil-adhesion-inducing activity was due both to a direct activation of neutrophils and to an influence of the sinusoidal endothelium itself by TNF: pretreatment of sinusoidal endothelial cells with TNF followed by thorough washing resulted in an increased neutrophil attachment. Protein synthesis by endothelial cells was not required. However, incubation of sinusoidal endothelium with TNF followed by anti-TNF antibody treatment abrogated the increased neutrophil adhesion. This suggests that TNF bound to sinusoidal endothelial cell surfaces was responsible for neutrophil adhesion. It is concluded that TNF by increasing granulocyte sticking to the endothelial lining of the liver sinusoids may play a significant role in endotoxin-induced inflammation of the liver as it is found in the septic state.