Hantavirus cardiopulmonary syndrome (HCPS) is an often-fatal acute viral infection that was first recognized in 1993. The viruses that cause HCPS are transmitted to man from wild rodents. More than 200 cases with 45% of them fatal have been reported in North America. In South America, HCPS is proving to be more common and just as lethal as its North American counterpart. The rodents that carry HCPS viruses in South America are different but related to those that carry HCPS viruses in North America. As of August 1998, Chile and Argentina combined have experienced about as many cases (228) as the US and Canada, and with a case-fatality rate of 50%. The viruses active in South America are quite similar to those in North America, but not the same. Both the North American and South American diseases have the potential to cause epidemics, because rodent populations can increase drastically in response to climatological and ecological changes. Up until recently, however, we could take some comfort in knowing that hantaviruses are transmitted solely from rodent to man, and that person-to-person transmission was unheard of. Thus, epidemics could be controlled if the public was given sufficient and helpful advice about how to avoid contact with wild rodents. In late 1996, an outbreak occurred in southern Argentina involving very clear examples of person-to-person transmission of HCPS. Especially affected were hospital workers who treated patients with HCPS. This result was completely unexpected and led to heightened concern about increased epidemic potential of HCPS in both North and South America. It is disturbing that we know virtually nothing about the mechanism of interpersonal transmission of the Argentine/Chilean virus, Andes virus. Safety practices in Argentina were not noticeably different from those in the US or elsewhere. In addition, extraordinary examples of "clustering" of cases in Argentina and Chile have emerged since that suggest that the Argentine outbreak of 1996 was not unique. In this application, we will conduct both epidemiology and laboratory studies to try to define exactly how Andes virus is transmitted in southern Chile. Specifically we will study populations for hantavirus antibodies and use questionnaires to establish what kinds of rodent or interpersonal exposures might result in Andes virus transmission. We will study the blood, urine and lung secretions of patients with HCPS to determine whether Andes virus is present in high quantities in bodily fluids. We will also determine what viruses other than Andes virus might be associated with HCPS in Chile. With the information learned from this proposal, we hope to be able to offer very specific advice about ways to reduce the risk of contracting the viruses that cause HCPS.