Andes virus (ANDV), a member of the genus Hantavirus, is a causative agent of hantavirus pulmonary syndrome (HPS) and is the only hantavirus known to be transmissible from person to person. HPS is found in North and South America and is often fatal. To test the virulence of ANDV in nonhuman primates, we exposed cynomolgus macaques to Andes virus, either intravenously or by aerosol. The monkeys did not manifest clinical disease but showed significant lymphocyte decreases between days 8 and 11 postexposure. All monkeys developed (1) both IgM and IgG antibodies against the viral nucleocapsid protein and (2) a neutralizing antibody response. By plaque assay, serum samples were negative for infectious virus, but by nonnested reverse transcriptase-polymerase chain reaction, viral S-segment genomes were detected in whole blood from 4 of 6 monkeys. This study is the first demonstration of infection of nonhuman primates by an HPS-causing virus.