Antibodies to different viruses and bacteria were measured in the cerebrospinal fluid (CSF) of six patients with herpes simplex virus encephalitis proven by brain biopsy and in five others with a presumptive diagnosis. Antibodies to herpes simplex virus but not to other organisms appeared in the CSF of all patients after the first weeks of the illness. Herpes simplex virus antibodies were not found in control CSF. The antibodies persisted in the CSF and the serum/CSF antibody ratio remained altered, 32:1 to less than 1:1, in all cases during the follow-up to 29 months or until death. The CSF albumin level was normal and the IgG index (formula: see text) elevated in four proven and three presumptive cases indicating a local antibody production; in four patients the findings were inconsistent. These results suggest that prolonged antigen stimulation is present in the central nervous system after acute herpes simplex encephalitis and that serological measurements combined with immunoglobulin and albumin determinations may provide a tentative but not definite diagnosis in some cases after the acute phase of encephalitis together with a method for follow-up of patients.