Penicillin has long been recognized as the antibiotic of choice for treatment of meningococcal infections, but clinicians have recently become concerned about the susceptibility of meningococci to penicillin and other antibiotics used in the management of meningococcal disease. Strains relatively resistant to penicillin (minimum inhibitory concentrations ranging from 0.1 mg/L to 1.28 mg/L) have been reported from a large number of countries, although the frequency with which such isolates are found varies widely. The mechanism of relative resistance to penicillin involves, at least in part, the production of altered forms of one of the penicillin-binding proteins. Although treatment with penicillin is still effective against these relatively resistant strains, there is evidence that low-dose treatment regimens can fail. beta-Lactamase production in meningococci is extremely rare but has been reported, and this finding is of great concern. Resistance to sulfonamides and rifampin is of particular concern in regard to the management of contacts of patients with meningococcal disease.