Ampicillin resistance in Haemophilus influenzae, an organism once thought to be universally susceptible to ampicillin, is increasing. It varies from one institution or community to another, and rates of 6.6% to 48% have been reported. The vast majority of resistant strains produce beta-lactamase, an enzyme that hydrolyzes the beta-lactam ring of ampicillin and other susceptible beta-lactam antibiotics. The beta-lactamase production is mediated by a gene contained on a plasmid (piece of extrachromosomal DNA). It is important for physicians and microbiologists to be aware that an infection such as meningitis or otitis media could be caused by ampicillin-resistant strain of H influenzae. Knowledge of the incidence of resistance for the institution or community is particularly pertinent in selection of empiric therapy.