The emergence and persistence of aerobic and anaerobic beta-lactamase-producing bacteria (BLPB) were investigated in 26 children treated with penicillin for otitis media or pharyngitis and in 28 nontreated control children. beta-Lactamase-producers were isolated in three (12%) of the treated children before therapy, in 12 (46%) seven to ten days after completion of therapy, in nine (35%) 40 to 45 days after therapy, and in seven (27%) 85 to 90 days after therapy. These organisms were present in three (11%) of the nontreated children, and the number of patients harboring BLPB stayed constant throughout the three-month follow-up. The predominant BLPB were Bacteroides species (Bacteroides melaninogenicus group, Bacteroides oralis, and Bacteroides oris-buccae), Staphylococcus aureus, Haemophilus influenzae, and Branhamella catarrhalis. The emergence and persistence of BLPB after penicillin therapy may have important implications for the antimicrobial management of infections of the upper respiratory tract.