Herpes simplex virus encephalitis (HSVE) has a reported mortality of 60 to 80%. Because of the recently published data on experience with the antiviral agent vidarabine, early diagnosis of this infection becomes imperative if enhanced therapeutic efficacy is to be achieved. At the present time the only way to diagnose HSVE with certainty is by brain biopsy. However, in cases with biopsy-proven HSVE, it has been shown that a rise in serum and cerebrospinal fluid (CSF) antibody titers to HSV, resulting in serum: CSF ratios of less than 20, may be diagnostic for HSVE. Three infants, aged 5, 7 and 12 months, are described. All of them presented with fever, convulsions and CSF pleocytosis which, together with computer tomography scan findings, were suggestive of meningoencephalitis. The diagnoses of HSVE were made by IPAMA (immunoperoxidase antibody to membrane antigen) for determination of HSV-specific IgG titers, and ELISA (enzyme-linked immunosorbent assay) for determination of HSV-specific IgM titers. All three infants had HSV-specific IgM in their serum, as well as HSV-specific serum IgG:CSF IgG ratios of less than 20. Two infants were treated with vidarabine with significant improvement in one and complete recovery in the other. Increased clinical awareness of HSVE symptoms, combined with the application of these rapid methods of diagnosis, might significantly improve the outcome of HSVE.