Five cases of apparent relapse of herpes encephalitis were investigated. All patients recovered after antiviral and corticosteroid therapy. Samples of CSF taken from the patients at intervals through the initial and subsequent encephalitic episode were examined. PCR amplification of a 351 bp sequence from the Herpesvirus simplex (HSV) thymidine kinase gene demonstrated the presence of HSV DNA in CSF taken during the initial encephalitic illness but not during the second encephalitic episode. Intrathecal synthesis of HSV antibody (HSV antibody index > 1.9) was observed in all cases following the first episode, and there appeared to be no significant increase in intrathecal antibody synthesis in the second episode. High levels of CSF myelin basic protein were found during the acute phases of both the initial and the subsequent encephalitic illnesses. These data suggest that at least in our series of five patients, relapse following HSE may not be due to active viral replication.