The pathogenesis of otitis media is poorly understood, and the events leading to bacterial invasion of the middle ear cleft and resulting inflammation are a matter of conjecture. While Streptococcus pneumoniae is the most frequent microbe cultured from acute, purulent middle ear effusions, it is infrequently cultured from nonsuppurative serous and mucoid effusion. To explore the possibility that nonviable pneumococci persisting in the middle ear cleft might produce mucosal inflammation, a solution of heat-killed pneumococci was placed in the middle ear cavity of experimental animals. Mucoperiosteal pathology which followed inoculation included an active, early subepithelial inflammatory response, metaplasia of the lining epithelium and later new bone formation. Thus, nonviable pneumococci are capable of producing middle ear inflammation, and it is possible that persistence of whole nonviable organisms or subcellular components in either middle ear effusion or mucoperiosteum may lead to continued middle ear inflammation or nonsuppurative otitis media.