To determine whether tobacco smoke contributes to the pathogenesis of acute otitis media, chinchillas were exposed to mainstream tobacco smoke or sham conditions (cigarettes not lit) in a Walton smoke exposure machine for 20-minute cycles two or three times daily. After 6 to 8 weeks of daily exposure, 12 chinchillas were nasally injected with Streptococcus pneumoniae, and 18 chinchillas were injected into both middle ears with nontypable Haemophilus influenzae. Smoke or sham exposures were continued for 2 to 4 weeks after injection. Otitis media developed in none of the 12 nasally injected chinchillas and in all 18 chinchillas whose middle ears were injected with nontypable Haemophilus influenzae. Persistence of middle ear effusion and persistence of nontypable Haemophilus influenzae in the middle ear effusion were not different between the smoke- and sham-exposed groups. This suggests that mainstream smoke exposure does not change the natural course of otitis media in the chinchilla model.