There is increasing evidence that herpes simplex virus type 1 (HSV-1) infections of the human brain may be chronic rather than acute in nature and that HSV-1 may be associated with various neurological and psychiatric deficits in man. Recent studies indicate that antiviral drug treatment is effective in reducing the mortality rate due to herpes simplex virus encephalitis (HSVE) but that there are behavioral, cognitive and neurological sequelae (e.g. memory loss, impaired motor function) among survivors. There is also evidence that HSV-1 may be associated, mabey even causally, in psychiatric and chronic progressive neurological disorders (e.g. schizophrenia, depressive psychoses, and senile dementia). Chronic HSV-1 infections of human or animal brains have been limitedly studied, especially in regard to changes in behavior subsequent to an initial infection. Using animal models, we will evaluate the long term behavioral, neurological and neuropathological sequelae in drugtreated (adanine arabinoside, acycloguanosine) survivors of acute HSVE and determine whether continuing viral presence or viral-induced immunopathology play a role in the evolution of these sequelae.