Branhamella catarrhalis has recently been recognized as an opportunistic respiratory pathogen. We tested 10 isolates recovered from patients with documented B. catarrhalis pneumonia and 15 colonizing isolates for their susceptibility to 19 antimicrobial agents and for their ability to produce beta-lactamase. Eight of ten disease isolates and 12 of 15 colonizing isolates produced a detectable beta-lactamase. The isolates that were negative for beta-lactamase were susceptible to all agents tested, including penicillin G. Although all strains were found to be susceptible to the majority of the newer agents by broth dilution testing, the most active new semisynthetic penicillin was azlocillin (MIC that inhibited 90% of strains, 0.5 micrograms/ml), and moxalactam had the greatest potency among the cephalosporins (MIC that inhibited 90% of strains, 0.06 micrograms/ml). Members of the first- and second-generation cephalosporins had only moderate activity. All disease isolates were susceptible to the aminoglycosides and to trimethoprim-sulfamethoxazole and resistant to vancomycin. The antibiotic susceptibilities of the disease isolates were not different from those of the colonizing strains. The results of standardized disk diffusion testing did not correlate well with those of dilution testing for penicillin or ampicillin. However, disk diffusion testing did predict susceptibility adequately for the remainder of the antibiotics tested.