Since 1980, we have observed an increased incidence of otitis media caused by Branhamella catarrhalis. The outcome of therapy of acute otitis media caused by this organism has been studied in a number of randomised clinical trials. 75% of isolates produced β-lactamase. Failure to sterilise B. catarrhalis- infected middle ear exudates occurred in 3 of 11 patients treated with amoxycillin or bacampicillin, 2 of 19 treated with cefaclor, but in no patients treated with co-trimoxazole (n = 10) or amoxycillin-clavulanic acid (Augmentin), [n = 9]. All treatment failures were associated with β-lactamase-producing strains of B. catarrhalis. The emergence of antibiotic-resistant strains of B. catarrhalis in acute otitis media indicates the need for a re-evaluation of initial antibiotic therapy of this infection. This may be particularly true for areas where there is a high incidence of strains which elaborate β-lactamase.