Large quantities of type I interferon were detected in the cerebrospinal fluid (CSF) collected at the onset of herpes encephalitis. This interferon was synthesized intrathecally and disappeared about 10 days after the beginning of neurological signs. In 12 cases of post-eruptive measles encephalitis and in four post-rubella encephalitis, type I interferon was present only in low amounts, or not found at all, even in the CSF collected early. The existence of an intrathecal synthesis of interferon during encephalitis provides a valuable contribution to both the early diagnosis of herpes encephalitis and the study of the pathogenesis of virus infection of the central nervous system (CNS).