Vaccines composed of pneumococcal capsular polysaccharides (PS) conjugated to outer membrane protein complex (OMPC) from Neisseria meningitides group B bacteria were tested in the chinchilla otitis media model. Monovalent (types 6B and 23F), bivalent (6B+23F), and tetravalent (6B+14+19F+23F) PS-OMPC conjugate vaccines elicited significant total serum antibody responses against all four PS. Type 6B vaccine elicited IgG, IgM, and IgA antibodies after a single dose and an anamnestic IgG response after a second vaccine dose on day 28. Type 6B and 19F vaccines prevented or greatly attenuated pneumococcal otitis media after direct middle ear challenge with the immunizing serotype, type 14 vaccine was not protective by this challenge route, and type 23F pneumococci were not sufficiently virulent in chinchillas to test vaccine effectiveness. The promising results with two serotypes suggest the PS-OMPC conjugates may be useful in human infants.