An experimental model of human fallopian tubes in organ culture was used to examine the ability of lipopolysaccharide (LPS) of Neisseria gonorrhoeae to damage the fallopian tube mucosa. Gonococcal LPS was purified by hot phenol-water extraction and sequential ultracentrifugation. This LPS was highly lethal for lead-sensitized mice and at a concentration as low as 6 pg/ml reproducibly gelled limulus amoebocyte lysate. Gonococcal LPS damaged fallopian tube mucosa in concentrations as low as 0.015 microgram/ml, a values less than the LPS concentration in organ culture medium surrounding fallopian tube mucosa that was damaged by gonococcal infection. The toxic effect of LPS was neutralized by polymyxin B. Gonococci were shown to elaborate blebs of outer membrane material that is likely to contain LPS. These studies suggest that gonococci elaborate LPS-containing material into their surrounding medium, that the LPS is capable of mediating damage to human fallopian tube mucosa, and that the production of mucosal damage requires the lipid A portion of the LPS molecule.