During the spring of 1993, a mysterious respiratory disease struck the Four Corners region of the southwestern United States. Persons who became ill were generally young and previously healthy before succumbing to an acute febrile illness that began with simple influenza-like symptoms and often culminated in death by pulmonary edema and cardiovascular collapse. With astonishing speed and efficiency, a collaborative team of federal, state, and local healthcare workers, including clinicians, epidemiologists, and laboratory scientists, identified a newly discovered species of hantavirus as the causative agent of the outbreak. In the ensuing 25 years, the epidemiology, virology, pathophysiology, clinical course, and treatment of hantavirus pulmonary syndrome have been the focus of ongoing research. Because of its rarity, and because of the need for early acute intervention in the face of precipitous decline, recognition of the unique laboratory profile of hantavirus pulmonary syndrome in the setting of a predisposing exposure history is of paramount importance.

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