The efficacy of a new third-generation cephalosporin, cefixime, in the treatment of acute otitis media resulting from infection with ampicillin-resistant, beta-lactamase-producing nontypable Haemophilus influenzae, was evaluated using the chinchilla animal model. The results showed that cefixime, administered in moderately low doses (8 mg/kg of body weight, two times per day), readily penetrated the chinchilla middle ear and rapidly sterilized the effusion. The data also suggest that the effusions were resolved more quickly in the cefixime-treated group compared with a group of animals treated with ampicillin or an untreated control group. No adverse side effects were noted in the cefixime-treated animals. The results of this study warrant the testing of cefixime for acute otitis media in the clinical setting.