In a blinded fashion, 165 serum samples from patients with biopsy-characterized acute and chronic renal diseases (ACRDs), 34 serum samples from patients with congenital renal diseases (CRDs), and 100 serum samples from healthy adults were assayed for immunoglobulin G (IgG), IgM, and IgA antibodies to Hantaan and Puumala viruses by enzyme immunoassay (EIA). Twenty-six percent (44 of 165) of ACRDs, 3% (1 of 34) of CRDs, and none (0 of 100) of the healthy serum samples were positive for hantavirus-specific antibodies (P < 0.001, Fisher's exact test). Thirty of 44 positive serum samples (68%) were from three groups: ie, acute tubulointerstitial nephritis (AIN), 20% (9 of 44); necrotizing glomerulonephritis (NG), 27% (12 of 44); and IgA nephropathy, 20% (9 of 44). The remaining 14 positive samples were from patients with a varied group of renal conditions. IgA antibody levels alone were elevated in 37%, IgG alone in 33%, IgM alone in 17%, and all three isotypes in 13% of the AIN-, NG-, and IgA-positive samples. These data indicate that three renal diseases account for approximately 68% of the hantavirus-positive sera tested and that serological evaluations should include all three isotypes of antibodies.