Infections due to Neisseria meningitidis are a major public health concern. In France, during 1999-2002, a total of 2167 clinical isolates of N. meningitidis from invasive infections were studied at the National Reference Center for Meningococci (Paris). Serogroup B strains were the most common (58%), followed by serogroup C strains (29%) and serogroup W135 strains (8%). Various phenotypes were observed, reflecting heterogeneity in the meningococcal population. Strains were susceptible to antibiotics currently used for treatment and chemoprophylaxis of meningococcal infections. However, the prevalence of meningococci with reduced susceptibility to penicillin is increasing. Such strains were heterogeneous and accounted for approximately 30% of isolates during this period, warranting continued surveillance of this phenomenon.