The incidence of persistent group A beta-haemolytic streptococci in tonsils, despite penicillin therapy, has increased in recent years. beta-Lactamase-producing organisms have previously been recovered from 74% of patients with persisting group A streptococci. We investigated the possibility that beta-lactamase-producing strains of Bacteroides spp. can protect streptococci from penicillin. A mixed infection was induced in mice in the form of a subcutaneous abscess involving a penicillin-susceptible group A streptococcus, and a beta-lactamase-producing strain of either Bact. melaninogenicus or Bact. fragilis. The infected animals were treated for seven days with parenteral penicillin, penicillin and clavulanic acid or clindamycin. Penicillin treatment prevented the formation of abscesses in animals inoculated with group A streptococci alone, but not in those inoculated with group A streptococci and Bacteroides spp. We attributed this resistance to penicillin therapy, and the subsequent formation of abscesses in mice, to protection of the streptococci from penicillin by beta-lactamase-producing strains of Bacteroides spp. Effective therapy for mixed infections was achieved when clavulanic acid, a beta-lactamase inhibitor, was administered with penicillin. A similar effect was noted with clindamycin, which is active against both group A streptococci and Bacteroides spp.