A cluster of deaths in 1993 in the southwestern U.S. that were characterized by an acute respiratory failure and shock were determined to be due to hantaviruses, which are RNA zoonotic viruses typically transmitted by a rodent vector. Given a fatality rate ranging from 15% to 40% and capacity to potentially spread through human-to-human contact, it is possible that the public health risks posed by these agents have been underestimated.