After an epidemic of serogroup A meningococcal meningitis in northern Ghana, a gradual disappearance of the epidemic strain was observed in a series of five 6-month carriage surveys of 37 randomly selected households. As serogroup A Neisseria meningitidis carriage decreased, an epidemic of serogroup X meningococcal carriage occurred, which reached 18% (53/298) of the people sampled during the dry season of 2000, coinciding with an outbreak of serogroup X disease. These carriage patterns were unrelated to that of Neisseria lactamica. Multilocus sequence typing and pulsed-field gel electrophoresis of the serogroup X bacteria revealed strong similarity with other strains isolated in Africa during recent decades. Three closely related clusters with distinct patterns of spread were identified among the Ghanian isolates, and further microevolution occurred after they arrived in the district. The occurrence of serogroup X outbreaks argues for the inclusion of this serogroup into a multivalent conjugate vaccine against N. meningitidis.