A guinea pig subcutaneous chamber model was used to evaluate the specificity of the immune response resulting from Neisseria meningitidis infection. Small numbers of meningococci easily infected the chambers. The infections persisted for 6-8 days with relatively high levels of organisms (10(5)-10(6)/milliliter) in the chambers, and were then rapidly eliminated and no organisms could be cultured beyond day 14. Clearance of infection correlated with appearance of circulating antibody. Antibody against both the protein serotype antigen and the capsular polysaccharide were induced as a result of meningococcal infection. The group-specific polysaccharide response peaked 2-3 wk after the animals were inoculated, while the type-specific protein response peaked at 5-6 wk. The animals were quite resistant to reinfection with either the homologous serogroup or serotype.