More than 90% of community hospital-isolated strains of Staphylococcus (including methicillin-resistant isolates), Streptococcus, Haemophilus, Neisseria, Branhamella, Bacteroides, Escherichia coli, Klebsiella, Enterobacter aerogenes, Proteus, and Acinetobacter calcoaceticus were inhibited by the sulbactam/ampicillin (1:2)combination at concentrations of 8 µg/16 µg per ml. The peak serum level from a 15-min infusion of I gl2 g of sulbactam/ampicillin is more than seven times this 90% end point. Excellent bactericidal activity was demonstrated against ampicillin-resistant isolates. Ampicillin-resistant strains did not develop resistance to sulbactam/ampicillin when they were serially transferred in the presence of sublethal concentrations of the combination. In mice the combination was active against a variety of acute, fatal infections produced by ampicillin-resistant bacterial isolates, including methicillin-resistantstrains of Staphylococcus aureus and mixed anaerobes. The in vitro and in vivo properties of sulbactam/ampicillin, coupled with its reliable pharmacokinetic performance, appear to make the combination ideally suited for the treatment of polymicrobial (aerobe-anaerobe) infections.