Meningococcal disease is normally suspected on clinical grounds but confirmed by isolation of Neisseria meningitidis from blood or cerebrospinal fluid (CSF), or by detection of gram-negative diplococci in CSF. After parenteral antibiotics are started the isolation rate of meningococci from blood cultures drops from 50% to less than 5% and the chances of CSF being positive by culture or microscopy are also reduced. We used the polymerase chain reaction (PCR) in a blinded study to detect meningococcal DNA in 54 CSF samples from patients with meningococcal disease or from controls. The PCR primers were specific for the meningococcal insertion sequence IS1106. The sensitivity and specificity of this PCR for diagnosis of meningococcal meningitis were both 91%. Sensitivity was not affected by prior antibiotic treatment. The IS1106 PCR is a rapid and sensitive test for confirmation of the diagnosis of meningococcal meningitis.