We have examined the distribution of type 1 herpes simplex virus (HSV-1) DNA in the brains of 8 humans surviving for between 4 months and 17 years after acute encephalitis. Histological examination showed neuronal loss and gliosis largely confined to the temporal and frontal lobes, typical of HSV-1 encephalitis. There was a widespread persistent inflammatory infiltrate, present in both the cerebrum and brainstem. Viral DNA was detected in paraffin sections of formalin-fixed paraffin-embedded autopsy brain by use of the polymerase chain reaction to amplify a fragment of the HSV-1 thymidine kinase gene. HSV-1 DNA was amplified from the cerebrum in 6/8 cases and from the brainstem in 4/8 cases. These findings suggest the possibility that HSV-1 may persist within the human central nervous system after acute herpes simplex encephalitis. The distribution of the viral DNA correlates better with that of the persistent inflammatory infiltrate than with the destructive lesions of the acute encephalitis.