PURPOSE: The primary goal of this study was to determine the viral cause of the acute retinal necrosis syndrome in 28 patients (30 eyes). A secondary goal was to investigate possible associations between viral cause and patient age, and viral cause and central nervous system disease. METHODS: A retrospective case series in which we reviewed the laboratory results and clinical histories of 28 patients (30 eyes) diagnosed with acute retinal necrosis syndrome, from whom vitreous or aqueous specimens were received, for diagnostic evaluation using previously described polymerase chain reaction- based assays. RESULTS: Varicella-zoster virus, herpes simplex virus, and cytomegalovirus (CMV) DNA were detected in aqueous and/or vitreous specimens from 27 of 28 patients (29 of 30 eyes with a clinical history of acute retinal necrosis syndrome). No sample was positive for DNA from more than one virus. Varicella-zoster virus DNA was detected in 13 patients (15 eyes). Median age was 57 years. Herpes simplex virus type 1 DNA was detected in seven patients (seven eyes). Median age was 47 years. Six of these patients had a history of herpes simplex virus encephalitis. Herpes simplex virus type 2 DNA was detected in six patients (six eyes). Median age was 20 years. Three of these patients had a likely history of meningitis. Cytomegalovirus DNA was detected in one patient who was immunosuppressed iatrogenically. No viral DNA was detected in one patient from whom a sample was taken after 6 weeks of acyclovir therapy. CONCLUSIONS: The data suggest that varicella-zoster virus or herpes simplex virus type 1 cause acute retinal necrosis syndrome in patients older than 25 years, whereas herpes simplex virus type 2 causes acute retinal necrosis in patients younger than 25 years. A history of central nervous system infection in a patient with acute retinal necrosis syndrome suggests that herpes simplex virus is likely to be the viral cause. (C) 2000 by Elsevier Science Inc.