The accuracy of computed tomography (CT) in the diagnosis of herpes simplex encephalitis (HSE) was assessed in 121 patients who during a 2 1/2 year period entered a prospective Swedish joint study with participation of six University Centres. The patients presented with symptoms and signs of febrile focal encephalopathy. The age ranged from 1 month to 76 years (mean 37.3 years). Only 6 were infants less than one year old. HSE was diagnosed in 50 patients by the demonstration of intrathecal HSV antibody production and/or by HSV isolation or antigen detection in brain tissue specimens. A total of 308 CT examinations--the majority performed during the first 5 days after onset of CNS symptoms--were evaluated under blind conditions. The correct diagnosis of HSE was usually suggested within 5 days after onset of neurologic symptoms yielding a sensitivity of 0.73 and a specificity of 0.89. Predominant location of the HSE lesions was the temporal lobes (88%), which rarely were involved in the non-HSE group (11%). Haemorrhage was a rare finding (12% ) and enhancement after intravenous contrast administration was insignificant. Repeat examinations further increased accuracy. It is concluded that the good reliability of high resolution CT, further improvement of immunologic techniques and the advent of new atoxic antiviral drugs all are factors which may in the future obviate the need for brain biopsy.