We analyzed the genotype for HLA-DRB1 alleles by digestion of polymerase chain reaction-amplified genes with the restriction endonucleases (PCR-RFLP) method to investigate the influence of HLA-DR antigen "splits" at the DRB1 gene level on the incidence of acute graft rejection in the renal transplant. For all patients, the incidence of acute rejection was proportional to the number of the serological HLA mismatch (0% in patients with two-haplotype match; 18% with HLA-A, -B, and -DR zero mismatch; 33% with HLA-DR zero mismatch; and 48% with HLA-DR one mismatch). For the patients with serological HLA-DR zero mismatch, the incidence of acute rejection in patients with HLA-DRB1 one mismatch (10/13: 77%) was significantly higher than that in those with zero mismatch (2/27: 7%). It was concluded that genotyping for HLA-DRB1 alleles would be beneficial in predicting acute rejection in patients with serological HLA-DR zero mismatch, although no difference was noted in the graft survivals.