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Since 1994, wildlife biologists and wildlife health specialists have worked to determine the cause of avian vacuolar myelinopathy (AVM), a neurologic disease of bald eagles (Haliaeetus leucocephalus) and other birds. The causes of morbidity and mortality in wildlife typically are determined through both antemortem and postmortem examinations, combined with ancillary tests for microbiological organisms, toxicants and other etiologies. However, the etiology of AVM has not been determined yet, despite extensive diagnostic investigations, including examinations for common disease agents, as well as infrequent or unusual causes of mortality. With the failure of standard diagnostic testing to determine the cause of AVM, investigations have evolved to include an ecosystem-oriented approach, conducted through the collaborative efforts of numerous state and federal wildlife resource agencies, universities, private foundations and other institutions.