The determinant(s) of gonococcal resistance to killing by human polymorphonuclear (PMN) phagocytes appear to be present in outer membrane vesicles (OMV) purified from lithium chloride extracts of Neisseria gonorrhoeae strain BS4 (agar) by wheat germ agglutinin (WGA) affinity chromatography. OMV neutralized the ability of antisera raised against whole gonococci to drastically reduce the capacity of strain BS4 (agar) to survive within PMN phagocytes. Furthermore, analysis by SDS-PAGE of OMV/WGA precipitates from lithium chloride extracts of strain BS4 (agar) and strain BSSH, which was more susceptible to phagocyte killing than strain BS4 (agar) and yielded OMV with poor antiserum-neutralizing activity, suggested that three proteins were associated with resistance to phagocyte killing.