S. pneumoniae, the primary bacterial pathogen of otitis media, continues to be a major cause of hearing loss in early childhood. Despite the established effectiveness of the pneumococcal polysaccharide vaccine in preventing pneumococcal pneumonia in adults, preliminary studies using an octavalent pneumococcal polysaccharide preparation have indicated that the vaccine is only marginally effective in preventing otitis media in infants. Recent studies have demonstrated that local secretory IgA antibody is secreted by goblet cells lining the middle ear and upper Eustachinan tube and it is now evident that certain bacterial species are capable of inducing a local antibody response. We have sought to take advantage of the temperature differential in the respiratory tract and have selected mutants of S. pneumoniae which grow vigorously at 32 degrees C, the temperature of the upper respiratory tract, but which do not replicate efficiently at the temperature of the lower respiratory tract, 37-38 degrees C. Mutants of this type would be able to replicate efficiently in the nasopharynx and stimulate the production of local antibody but would not retain the capacity to produce disease in the lower respiratory tract because of their failure to grow to high titer at the restrictive temperature.