The prevalence of plasmid-mediated beta-lactamase production among clinical isolates of Haemophilus influenzae has increased globally since this characteristic was first recognized in 1972. Three nationwide surveillance studies conducted in the United States in the 1980s indicated that the rate of beta-lactamase production was approximately 30% among serotype b isolates and approximately 15% among nonencapsulated strains. The American studies also documented strains with resistance to chloramphenicol, tetracycline, trimethoprim-sulfamethoxazole, rifampin, erythromycin, and certain older cephalosporins. Surveillance studies performed at about the same time in Canada, Europe, the United Kingdom, and several developing countries have also documented the prevalence of beta-lactamase-producing isolates and resistance among them to alternative agents such as chloramphenicol and tetracycline. Perhaps of greatest concern has been the isolation of H. influenzae (both serotype b and nonencapsulated strains) in the United States, Europe, and Asia that possess multiple antimicrobial resistance mechanisms. At the present time, H. influenzae isolates have not been detected that are resistant to either third-generation cephalosporins or fluoroquinolones.