Soluble HLA enzyme-linked immunosorbent assays (ELISAs) for the detection of anti-HLA class I immunoglobulin G (IgG), IgG1, IgG2, IgG3, IgG4, IgM, and IgA antibodies were developed and used to analyze retrospectively the correlation between pretransplant allosensitization and posttransplant rejection episodes in renal allograft recipients. Enzyme-linked immunosorbent assay plates were coated with 46 different soluble HLA preparations representing 40 different HLA class I antigens. After incubation with a serum specimen, bound antibodies were detected with a peroxidase-conjugated antibody. Serum specimens from 85 patients were analyzed. All patients tested positive by microlymphocytotoxicity (ie, >5% panel-reactive antibody [PRA]). Approximately half (56%) of the patients had experienced one or more rejection episodes within 12 months posttransplantation. Fifty-five patients tested positive by ELISA (total IgG %PRA >10%). A strong correlation between first-year rejection and ELISA-detected anti-HLA class I IgG1 was observed (P = 0.0004). The predictive value for IgG1 and first-year rejection was 77.5%, demonstrating that ELISA results identify patients at high risk of rejecting the transplanted kidney. Anti-HLA class I total IgG detected by ELISA also correlated with first-year rejection episodes (P = 0.04). The presence of anti-HLA class I IgG2, IgG3, IgG4, or IgM was not predictive of first-year rejection episodes. Anticlass I IgA antibodies were only found in combination with anti-class I IgG1 antibodies.