fatal hemorrhagic fever caused by west nile virus in the united states background most west nile virus wnv infections in humans are asymptomatic severe disease occurs in relatively few patients and typically manifests as encephalitis meningitis or acute flaccid paralysis a few cases of lifethreatening disease with diffuse hemorrhagic manifestations have been reported in africa however this clinical presentation has not been documented for any of the 16700 cases of wnv disease reported in the united states during 19992004 we describe a case of fulminant wnv infection in a 59yearold florida man who died following a brief illness that resembled hemorrhagic disease caused by rickettsia reckettsii dengue virus or yellow fever virusmethods traditional and contemporary diagnostic assays including culture isolation electron microscopic examination reversetranscriptase polymerase chain reaction amplification and immunohistochemical stains were used to confirm systemic wnv infection in the patientresults wnv was isolated in a cell culture from a skin biopsy specimen obtained from the patient shortly prior to death electron microscopic examination identified the isolate as a flavivirus and reversetranscriptase polymerase chain reaction amplified specific wnv sequences from the isolate and patient tissue quantitative polymerase chain reaction identified approximately 1x107 viral copiesml in the patients serum wnv antigens were detected by immunohistochemical stains in intravascular mononuclear cells and endothelium in skin lung liver kidney spleen bone marrow and central nervous system no viral antigens were identified in neurons or glial cells of the central nervous systemconclusions although hemorrhagic disease is a rare manifestation of wnv infection the findings provided by this report may offer new insights regarding the clinical spectrum and pathogenesis of wnv disease in humans