Clinical isolates of the Bacteroides melaninogenicus and Bacteroides fragilis groups were tested for in vitro and in vivo susceptibility to penicillin, clindamycin, and metronidazole, used singly or in combination with gentamicin. The in vitro tests consisted of determinations of minimal inhibitory concentrations (MICs) carried out with or without constant amounts of gentamicin. When used alone, gentamicin had negligible effects on the bacteria but significantly reduced the MICs of penicillin, clindamycin, and metronidazole against 11, 10, and 3, of the 15 strains of the B. melaninogenicus group, respectively. The 15 strains of the B. fragilis group were all P-lactamase producers and were highly resistant to penicillin or the combination of penicillin and gentamicin. However, gentamicin reduced the MICs of clindamycin and metronidazole against 1 and 7 strains of this group, respectively. The in vivo tests were carried out in mice and consisted of measurements of the effects of the antimicrobial agents on the sizes and bacterial content of abscesses induced by subcutaneous injection of bacterial suspensions. This work was prompted by the need to extend the abovedescribed observations on drug synergism to other antibacterial combinations and to strains of the B. melaninogenicus group. We show that, with many strains, gentamicin, which by itself has a negligible inhibitory effect on Bacteroides spp., is very effective in combination with penicillin, clindamycin, or metronidazole in reducing the minimal inhibitory concentrations (MICs) of these antimicrobial agents and in suppressing abscess formation in infected mice.(The experiments conducted herein were carried out in accordance with the principles set forth in the Guide for the Care Tables 1 and 2). All strains were encapsulated as confirmed by the Hiss staining method (14) and by electron microscopy after staining with ruthenium red (9). Stock suspensions were stored in skim milk at -70°C. For the experiments described here, the bacteria were grown anaer- obically on blood agar plates with a brain heart infusion base (Difco Laboratories, Detroit, Mich.) for a total of two or three passages after isolation.Animals. Male Swiss albino mice weighing 20 to 25 g each were obtained from the Naval Medical Research Institute mouse colony. The mice were raised under conventional conditions. Antimicrobial agents. The following antimicrobial agents, obtained from the indicated sources, were used: penicillin G, E. R. Squibb & Sons, Inc., Princeton, N.J.; clindamycin, The Upjohn Co., Kalamazoo, Mich.; metronidazole, G. D. Searle & Co., Chicago, Ill.; and gentamicin, Schering Corp., Kenilworth, Ill. MICs were determined by the agar dilution method (19) with a series of nine concentrations of each agent. Each experiment was repeated twice. For penicillin G, the concentrations were 12, 6, 3, 1.5, 0.75, 0.2, 0.1, 0.05, and 0.01 ,ug/ml, except that concentrations of as high as 64 pug/ml were used in preliminary tests with strains of the B.fragilis group. For clindamycin, metroni...