The unusually high 88% one-year cadaver kidney graft survival rate in patients with IgA nephropathy (IgAN) prompted us to investigate the influence of IgA anti-HLA class I antibodies on subsequent graft survival. We found that patients with various original diseases with IgA antibodies to the HLA molecule had high 91% one-year graft survival compared with 58% one-year survival for those who did not have preformed IgA antibodies against the HLA molecule prior to transplantation (P < 0.0005). The IgA antibodies were detected by reaction with class I HLA molecules isolated by capture with monoclonal antibody and detected with an enzyme-linked immunosorbent assay. In contrast, IgG antibodies to the HLA molecule resulted in a lower one-year graft survival rate (74%) than in those patients without IgG antibodies (87%) (p = 0.08). IgA antibodies to the HLA molecule, when present, tended to react at a high frequency on a random lymphocyte panel. These findings suggest that sensitization resulting in IgA anti-HLA antibodies may counteract the deleterious effect of an IgG antibody response in clinical kidney transplantation.