In Niger, epidemic meningococcal meningitis is primarily caused by Neisseria meningitidis (Nm) serogroup A. However, since 2002, Nm serogroup W135 has been considered to be a major threat that has not yet been realized, and an unprecedented incidence of Nm serogroup X (NmX) meningitis was observed in 2006. Meningitis surveillance in Niger is performed on the basis of reporting of clinically suspected cases. Cerebrospinal fluid specimens are sent to the reference laboratory in Niamey, Niger. Culture, latex agglutination, and polymerase chain reaction are used whenever appropriate. Since 2004, after the addition of a polymerase chain reaction-based nonculture assay that was developed to genogroup isolates of NmX, polymerase chain reaction testing allows for the identification of Nm serogroup A, Nm serogroup B, Nm serogroup C, NmX, Nm serogroup Y, and Nm serogroup W135. From January to June 2006, a total of 4185 cases of meningitis were reported, and 2905 cerebrospinal fluid specimens were laboratory tested. NmX meningitis represented 51% of 1139 confirmed cases of meningococcal meningitis, but in southwestern Niger, it represented 90%. In the agglomeration of Niamey, the reported cumulative incidence of meningitis was 73 cases per 100,000 population and the cumulative incidence of confirmed NmX meningitis was 27.5 cases per 100,000 population (74.6 cases per 100,000 population in children aged 5-9 years). NmX isolates had the same phenotype (X : NT : P1.5), and all belonged to the same sequence type (ST-181) as the NmX isolates that were circulating in Niamey in the 1990s. Nm serogroup W135 represented only 2.1% of identified meningococci. This is, to our knowledge, the first report of such a high incidence of NmX meningitis, although an unusually high incidence of NmX meningitis was also observed in the 1990s in Niamey. The increasing incidence of NmX meningitis is worrisome, because no vaccine has been developed against this serogroup. Countries in the African meningitis belt must prepare to face this potential new challenge.