Cases of human hantavirus disease have been reported in Chile since 1995, most of them in people living in rural and periurban areas. We conducted a peridomestic study of small mammals to evaluate the relationships between the presence of rodents with antibodies to Andes virus confirmed human cases of hantavirus pulmonary syndrome in southcentral Chile. The results of 20 sampled sites, which involved the capture of 272 mice over ah 18-month period, showed the occurrence of 10 small mammal species, of which Oligoryzomys longicaudatus was the only sero-positive species for hantavirus, with an intra-specific serologic rate of 10.4%.