Several species of Hantavirus (family Bunyaviridae) can cause disease in humans, but in the United States, Sin Nombre virus is the most notorious and severe. Sin Nombre virus was first reported in 1993 in the Four Corners region of the southwestern United States (Arizona, Colorado, New Mexico, Utah). Physicians working for the Indian Health Service in that region noted a cluster of young healthy persons who developed severe respiratory illnesses characterized by rapidly progressive, noncardiogenic pulmonary edema, and a high case fatality rate. Though it was first clinically detected in the United States in 1993, retrospective serologic data as early as 1959 indicates that Sin Nombre virus was present decades earlier. From 1993 to 2005, 396 cases of hantavirus pulmonary syndrome (HPS) were reported in the United States, with 20 to 50 cases occurring annually.

The epidemiology of HPS in the United States usually affects healthy adults (mean age 38 years) residing in rural areas. Approximately 77% of affected patients are Caucasian and 19% American Indian. Hantaviruses are transmitted to humans by rodents via aerosolization of infected excreta. While contaminated urine is most commonly implicated, rodent droppings, saliva, and nesting materials can also aerosolize to cause illness. Rarely, hantaviruses may also be transmitted through direct mucous-membrane contact or inoculation. These viruses do not cause apparent illness in their rat reservoirs. Several murine species can transmit hantaviruses, but in the United States, deer mice (Peromyscus maniculatus) are the primary reservoir for Sin Nombre virus. The cotton rat, rice rat, and white-footed mouse transmit other hantavirus species in the United States. Therefore, given that there is neither an effective vaccine nor therapy, the primary strategy for combating HPS is rat control. No human-to-human cases have been reported, nor have pets or farm animals been implicated in disease transmission.