Antibiotic susceptibilities of Pasteurella sp, Haemophilus pleuropneumoniae, and Staphylococcus aureus isolates were determined. The combination of sodium sulbactam, a beta-lactamase inhibitor, and ampicillin had a synergistic effect against all ampicillin-resistant pathogens, rendering them susceptible to ampicillin. Studies of cell-free beta-lactamase from Pasteurella and Haemophilus isolates confirmed the presence of a constitutive penicillinase. Inhibitory concentrations of sulbactam-ampicillin were bactericidal, as demonstrated by killing curves. Ampicillin-resistant Pasteurella and Haemophilus isolates did not develop resistance to sulbactam-ampicillin when passed as many as 8 times in the presence of sublethal concentrations of sulbactam-ampicillin. The in vitro synergistic activity of sulbactam-penicillin also was seen in an in vivo synergistic response in mice challenge exposed to an ampicillin-resistant P haemolytica.