We investigated the possibility that beta-lactamase producing strains of Klebsiella pneumoniae and Staphylococcus aureus can protect organisms of the Bacteroides melaninogenicus group from penicillin. A mixed infection was induced in mice in the form of a subcutaneous abscess involving a penicillin-susceptible encapsulated B. melaninogenicus, and a beta-lactamase producing strain of either K. pneumoniae or S. aureus. The infected animals were treated for 7 days with single or combined antimicrobial therapy. The single agents used were penicillin, clavulanic acid, metronidazole, and gentamicin. The antimicrobial combinations were penicillin and clavulanic acid, penicillin and gentamicin, and metronidazole and gentamicin. Administration of a single agent was effective in treating abscesses caused by susceptible organisms. The only effective therapy for mixed infections was by combination therapy of penicillin and clavulanic acid or metronidazole and gentamicin. This study supports the hypothesis that beta-lactamase producing facultative bacteria may shield their anaerobic counterparts from penicillin therapy, thereby contributing to the persistence of the infection.