Hantavirus cardiopulmonary syndrome (HCPS) is an acute viral infection with a 50% case-fatality that was first recognized in 1993 in New Mexico. Wild rodents transmit it to man. Both North and South America have experienced outbreaks and sporadic cases of HCPS, with 500 cases now recognized. University of New Mexico (UNM) faculty are leaders in the study of HCPS and its ecology, diagnosis, molecular biology, vaccine development, treatment, and pathogenesis. They have traveled to 5 countries in South America, Europe, Israel and Australia to teach courses and conduct workshops, and several have served on NIH and CDC committees on HCPS. UNM currently holds more than $1 million/year in direct costs in federal grants that are directed solely in hantavirus research, as well as other large grants with a hantavirus component. This application describes an International Collaboration in Infectious Diseases Research (ICIDR) program for hantavirus research that matches UNM expertise and resources with similar impressive expertise and resources in Chile. Chilean collaborators are in Santiago at the federal Ministry of Health, including its laboratory branch, the Institute of Public Health (ISP); at Catholic University and University of Chile; and at regional hospitals in Coyhaique and Temuco, two of the primary sites at which HCPS patients are treated. Highly qualified and well-trained collaborators have been identified at all sites. The Ministry of Health rapidly developed resources and manpower to address the HCPS outbreaks, which were first recognized only in August 1997. They have constructed a new laboratory for biological containment work involving the very dangerous Andes hantavirus strain at the ISP and have secured a steady funding stream of $600,000/year from the federal government solely for hantavirus prevention and treatment. Most of these monies can be considered matching funds for the present application. The application involves 4 very strongly linked projects on the ecology of hantaviruses in wild rodents, the interpersonal transmission of HCPS, the genetic basis for severe HCPS and the treatment of HCPS. Two other US universities also provide specific research expertise. Each project pairs strong US technology and experience with highly motivated and experienced Chilean collaborators. Each project has clear and achievable specific aims that will advance the field considerably. A major goal of each project is the rapid and early transfer of technology to Chile to advance scientific knowledge about HCPS for the mutual benefit of both Chilean and US public health. The projects will foster Chilean science well beyond the hantavirus research arena. This ICIDR application is uniquely situated to produce a tremendous return in scientific knowledge because of the substantial cost-matching in Chile and the US and because there is currently relatively little knowledge regarding hantavirus ecology, transmission, disease causation, and treatment.