The in-vitro activity of various beta-lactam antibiotics, beta-lactam/beta-lactamase inhibitor combinations, clindamycin, and metronidazole was determined against Bacteroides fragilis group isolates that were resistant to both cefoxitin and cefotetan. Among the cephalosporins tested ceftizoxime was the most active with 80% of the strains susceptible, followed by cefotaxime (65% susceptible), and cefoperazone (47% susceptible). Piperacillin and clindamycin showed comparable activity to ceftizoxime with 80% and 81% susceptible, respectively. The addition of a beta-lactamase inhibitor (sulbactam, clavulanate, or tazobactam) enhanced the activity of the various beta-lactam agents from 4-fold to 16-fold overall. One strain of B. fragilis was found that was resistant to all beta-lactam agents either alone or in combination. All strains in this study were susceptible to less than or equal to 4 mg/l of metronidazole.