Subcutaneous chambers were implanted in mice, injected with Neisseria gonorrhoeae, and supplemented with complement as a model for studying the immunogenicity and strain diversity of N. gonorrhoeae. Immunotypic resistance to N. gonorrhoeae in immunized mice was significantly (P less than 0.01) increased by injection of exogenous guinea pig complement into the host before challenge with gonococci. By using this model to test gonococcal isolates from various geographical areas, two highly immunogenic but immunotypically different gonococcal strains were identified. The piliated cells of these strains induced both complement-enhanced immunity and a degree of exogenous complement-independent immunity. The immunity in mice not treated with complement developed more slowly, was less effective, and waned earlier than that which was complement-dependent. Pretreatment with complement, although highly effective in preventing infection in immunized mice, was much less beneficial in terminating already established infections, even though bactericidal antibodies were present at the time of complement treatment. The mouse chamber model in which both complement-mediated and complement-independent mechanisms of protection can be evaluated may provide an additional tool for elucidating the immunology of gonococcal or other microbial infections.