The natural history of experimental pneumococcal otitis media (POM) was studied in chinchillas following direct inoculation of Streptococcus pneumoniae into the middle ear cavity and following nasal colonization with S pneumoniae. POM was induced in over 75% of animals whose middle ears were inoculated with fewer than 1.5 x 10(2) S pneumoniae of types 3, 6A, 7F, 18C and 23B. Following nasal inoculation of pneumococci, fewer than 10% of animals spontaneously developed 50% of animals developed POM. Bacteriologic results suggested that POM induced by nasal colonization was less severe than that induced by direct middle ear inoculation, yet serum pneumococcal antibody responses were similar. These findings demonstrate the combined roles of nasopharyngeal colonization with pathogenic bacteria, compromised middle ear ventilation and immunologic response in the pathogenesis of otitis media. To determine whether pneumococcal capsular polysaccharide vaccine was effective in preventing experimental POM, 23 chinchillas were vaccinated with type 7 pneumococcal vaccine. Fourteen animals seroconverted with at least a twofold rise in serum antibody, and nine did not seroconvert. Following intranasal inoculation of type 7 S pneumoniae and application of bilateral negative middle ear pressure, only one (7%) of the vaccinated seroconverting animals and four (44%) of the nonseroconverting animals developed POM. Twenty-six of 42 (62%) unvaccinated animals developed POM. Protection was associated with high levels of serum antibody prior to nasal inoculation, and higher antibody levels were found in sterile middle ear effusions than in effusions with pneumococci. These findings suggest that vaccination with pneumococcal capsular polysaccharide may be effective for preventing type-specific pneumococcal otitis media in infants and young children.