Cefoperazone, a cephalosporin which inhibits most Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus, is hydrolyzed by some β-lactamases. Combination of cefoperazone with β-lactamase inhibitors, clavulanic acid and penicillanic acid sulfone, inhibited Escherichia coli, Klebsiella spp. and Bacteroides fragilis and other enteric organisms which were resistant to cefoperazone. Clavulanic acid acted synergistically with cefoperazone inhibiting 66% of resistant isolates. Although penicillanic acid sulfone also acted synergistically with cefoperazone against β-lactamase containing organisms, clavulanic acid was synergistic at lower concentrations. The β-lactamase inhibitors did not increase cefoperazone's activity against Pseudomonas spp. Combination of cefotaxime, a type I β-lactamase inhibitor, with cefoperazone did not increase the activity of the two agents and in some instances showed antagonism.