We performed a prospective study to monitor changes in the bacterial etiology of acute otitis media. Branhamella catarrhalis was isolated from middle ear exudates of 3 of 47 children (6.4%) studied between September 1979 and September 1980 and from 26 of 98 children (26.5%) studied between October 1980 and February 1982 (P = 0.0055). Twenty of 26 B. catarrhalis strains (76.9%) were found to be resistant to ampicillin and to produce beta-lactamase. In contrast only 2 of 26 strains of Haemophilus influenzae (7.7%) isolated from the same group of patients were resistant to ampicillin. We could not detect changes in culture methods, in demographic features, in patterns of medical care or in prior middle ear disease or antimicrobial drug usage,-which might explain this striking increase in the relative importance of resistant strains of B. catarrhalis.