Between 1993 and 1998, 10 cases of clinical hantavirus infection were diagnosed in Brazil. Hantavirus-specific IgM, or positive immunohistochemical analysis for hantavirus antigen, or positive reverse transcription-polymerase chain reaction results for hantavirus RNA were used to confirm nine of these cases; eight were hantavirus pulmonary syndrome (HPS), and one was mild hantavirus disease. The remaining clinical case of hantavirus infection was fatal, and no tissue was available to confirm the diagnosis. During the first 7 months of 1998, five fatal HPS cases caused by a Sin Nombre-like virus were reported from three different regions in the State of São Paulo, Brazil: two in March (Presidente Prudente Region), two in May (Ribeirão Preto Region), and one in July (Itapecerica da Serra Region). Epidemiologic, ecologic, and serologic surveys were conducted among case contacts, area residents, and captured rodents in five locations within the State of São Paulo in June of 1998. Six (4.8%) of 125 case contacts and six (5.2%) of 116 area residents had IgG antibody to Sin Nombre virus (SNV) antigen. No case contacts had a history of HPS-compatible illness, and only one area resident reported a previous acute respiratory illness. A total of 403 rodents were captured during 9 nights of trapping (1969 trap nights). All 27 rodents that were found to be positive for IgG antibody to SNV antigen were captured in crop border and extensively deforested agricultural areas where four of the 1998 HPS case-patients had recently worked. The IgG antibody prevalence data for rodents suggest that Bolomys lasiurus and perhaps Akodon sp. are potential hantavirus reservoirs in this state of Brazil.