Objectives: The pathogenesis of subacute sclerosing panencephalitis (SSPE), and particularly, the cause of measles virus (MV) reactivation following a latent period after primary measles infection is unknown. The hypothesis of other viruses contributing to the pathogenesis of SSPE by affecting the in vivo state of MV was investigated. Methods: We examined the cerebrospinal fluid of SSPE patients (n = 43) for DNA or RNA and antibodies against HSV type 1 and 2, EBV, CMV, VZV, Hepatitis B, Hepatitis C, JC virus, human herpesvirus (HHV)-6, HHV-7, HHV-8, HTLV-1, and HTLV-2. We compared the findings with those of patients with other neurological disorders (n = 39). Results: CMV DNA and HSV type 1 IgG were found more frequently in SSPE patients. Other positive results were at similar incidence in SSPE and control groups. The clinical features of SSPE cases with and without positive viral tests did not differ from each other. Conclusion: These data do not support a specific role for these agents in SSPE, but imply that the passage of some viruses to the CNS and local antibody synthesis may be facilitated by inflammation. The persistence or reactivation of MV in SSPE may be related to other factors pertaining to the host or environment. © 2002 The British Infection Society.