An in vivo typing system for studying the immunological relationship of gonococcal strains was established. Nine gonococcal strains of proven virulence for guinea pig subcutaneous chambers were selected, and these isolates were used to immunize groups of guinea pigs that were subsequently cross-challenged with graduated numbers of gonococci from these isolates. Resistance to infection was determined by culture of fluid from challenged chambers; results were expressed as the median dose, in colony-forming units, of gonococci required to produce infection in each group of immunized guinea pigs. This information was then used to develop immunotypes of gonococci based on the cross-protection results obtained. Four cross-protecting immunotypes were established from the preliminary nine strains tested.