The expression of adhesion molecules on human vascular endothelial cells (EC) during infection or inflammation is necessary to initiate migration of leukocytes to the disease focus. Various bacteria or endotoxins (lipopolysaccharide, LPS) might exert differential capacity to induce adhesion molecules in endothelial cells. Therefore, we first investigated induction of adhesion by bacteria. Heat-killed Gram-negative bacteria (Escherichia coli) induced adhesion, whereas the Gram-positive Bacillus subtilis and Staphylococcus epidermidis or Mycobacterium tuberculosis did not, indicating the significance of LPS for this activation. Purified S-form LPS stimulated endothelial cells to express adhesion molecules for polymorphonuclear cells (PMN) or lymphocytes in a dose-dependent fashion. S-form LPS, containing an 0-specific chain, induced a maximal level of adhesion, comparable to adhesion induced by interleukin-1 (IL-1). We obtained the same results in cell ELISA with anti-ICAM-1 antibody (84H10). R-form LPS and free lipid A, lacking an O-specific chain also stimulated adhesion, however, to a lower degree (39-60%). Synthetic lipid A precursor Ia (compound 406) or another LPS-antagonist (non-toxic Rhodobacter capsulatus LPS) did not trigger endothelial cells to express adhesion molecules. These antagonists specifically inhibited LPS- or free lipid A-, but not IL-1-induced adhesion. These results suggest that lipid A is the active structure of LPS necessary for induction of adhesion, that the oligosaccharide portion is important for the capacity of LPS to stimulate adhesion, and that activation of adhesion to endothelial cells by LPS requires specific LPS binding sites.