Objective: To investigate the effects of the virulence characteristics of specific pneumococcal proteins on the inner ear. Main Outcome Measures: A histologic comparison of inflammatory cell infiltration and pathologic changes in the round window membrane and inner ear. Results: Most of the animals inoculated with highdose pneumolysin or wild-type bacteria showed severe pathologic changes of the inner ears. The inner ears of most animals inoculated with surface protein A or surface antigen A-deficient bacteria appeared normal. Conclusions: Pneumococcal surface protein A and pneumococcal surface antigen A are 2 important virulence factors in inner ear damage secondary to pneumococcal otitis media. Mutation of these virulence factors results in less inner ear damage. ©2009 American Medical Association. All rights reserved.