Antibody-mediated rejection (AMR) is now widely recognized as a major problem in organ transplantation. This study was conducted to investigate the relationship between newly developing anti-HLA antibodies post-transplantation (de novo Abs) and the outcome of living related kidney transplantation (LRKT). The subjects included 87 patients who had received living donor kidney allografts at our institution. Panel reactive Ab assay (Flow-PRA) and graft biopsies were performed in all the recipients before and 6 months after the LRKT. The incidence of AMR, the donor specificity and time of appearance of the de novo Abs were retrospectively studied. Among the 87 LRKT recipients, 47 (54%) showed negative/negative (N/N) results, 15 (17%) showed positive/positive (P/P) results, 12 (14%) showed positive/negative results (P/N), and 13 (15%) showed negative/positive (N/P) results (de novo Abs) in the pre-/post-transplant Flow-PRA analysis. Among the 13 cases with de novo Abs, 5 (38%) had donor-specific Abs (DSA) and the remaining 8 (62%) had nondonor-specific Abs, as determined by LAB single antigen analysis. Eighty percent of the recipients with DSA showed evidence of AMR in the graft biopsies. The 5-year graft survival rate of the recipients with de novo Abs (N/P) was 69%, as compared with 96% in the N/N, 88% in the P/N and 93% in the P/P recipient groups (P = 0.009). LRKT recipients developing de novo Abs, especially those with DSA, showed a much higher incidence of AMR and a worse prognosis. Cautious monitoring for the appearance of anti-HLA Abs should be adopted after transplantation, even in patients without anti-HLA Abs prior to the transplantation.