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Although exceedingly rare, fulminant hepatic failure (FHF) in immunocompetent patients can develop with primary or recurrent infection due to herpes simplex virus (HSV). The diagnosis is frequently obscured by the absence of mucocutaneous involvement. Elevated transaminase values with leukopenia and a relatively low bilirubin level may provide clues to the diagnosis. We describe an immunocompetent woman who died of FHF before a definitive diagnosis of HSV type 2 hepatitis was established. Herpes simplex virus hepatitis is one of the few causes of FHF for which potentially effective therapy is available. Thus, early diagnosis is paramount and usually requires liver biopsy. Recent studies suggest that transjugular liver biopsy is safe and effective in establishing the cause of FHF. Since the diagnosis and management of FHF are frequently influenced by the results of transjugular liver biopsy, it may become a standard diagnostic tool for managing FHF in centers where such expertise exists.