Hantavirus Pulmonary Syndrome (HPS), a severe and frequently fatal respiratory disease, was first recognized in 1993 during an outbreak of acute illness in the Four Comers area of the southwestern United States. The etiologic agent, Sin Nombre virus (SNV), was identified as a previously unrecognized member of the Hantavirus genus transmitted by rodents, especially members of the genus Peromyscus, which shed SNV in urine and feces. Since 1993, 16 California residents have been diagnosed with HPS, four of these were identified retrospectively with onset prior to 1993. The median age of case-patients was 42 years, 10 were male, and 8 died. Sites of likely exposure for these cases tended to cluster in the eastern Sierra Nevada range. Serologic surveillance of rodents has been conducted prospectively in California since 1993 and retrospectively for specimens collected back to 1975. To date, serologic evidence of infection with SNV has been recognized in 473 (6.6%) of 7,191 rodents from 18 genera, and in 426 (9.6%) of 4,489 Peromyscus spp. At least one seroreactive Peromyscus sp. specimen has been identified in 40 of 46 counties surveyed.