Amino acids within the HLA class I and II molecules were first examined individually for correlation with antibody reactions of over 50,000 antisera. The amino acids that correlated with the serologic reactions were classified as serologically defined: approximately half of the amino acids fell within that category, and the other half were employed as controls. The cadaver donor kidney transplant survival for patients who were mismatched for each of the sera-defined amino acids were compared to mismatches of the nonserologically defined amino acids. No differences were noted in the graft survivals of patients with mismatches for the serologically defined amino acids of HLA-A, -B, and -DR loci and for the nonserologically defined amino acids. Since many of the patients also had additional amino acids of mismatch, we cannot yet conclude that the serologically defined amino acids do not significantly influence graft outcome. In other words, the test may not have been sensitive enough to detect the degree of immunogenicity that may exist. However, we can conclude that mismatches for no single amino acid are strongly immunogenic.