Lipopolysaccharide (LPS) is a major surface component ofChlamydia trachomatis, as with all Gram-negative bacteria. The effect ofC. trachomatisLPS onC. trachomatisinfectivity of human epithelial cells was investigated.C. trachomatisLPS andC. trachomatisLPS antibody significantly reduced infectivity, mostly in a dose-dependent manner. As the structure of LPS inC. trachomatisis simple and consists only of lipid A and 3-deoxy-d-manno-octulosonic acid (Kdo), we investigated whether lipid A or Kdo was inhibitory to chlamydial infectivity. Polymyxin B, as a lipid A inhibitor, and Kdo considerably reducedC. trachomatisinfectivity. With all the LPS inhibitors used, there was greater inhibition against serovar E than serovar LGV. These results suggest a role for LPS in chlamydial infectivity. Elucidation of how LPS acts in infectivity and identification of host-cell receptors would help in understanding pathogenicity.