Amyloid fibrils formed from initially soluble proteins with diverse sequences are associated with an array of human diseases. In the human disorder, dialysis-related amyloidosis (DRA), fibrils contain two major constituents, full-length human beta(2)-microglobulin (h beta(2)m) and a truncation variant, Delta N6 which lacks the N-terminal six amino acids. These fibrils are assembled from initially natively folded proteins with an all antiparallel beta-stranded structure. Here, backbone conformations of wild-type h beta(2)m and Delta N6 in their amyloid forms have been determined using a combination of dilute isotopic labeling strategies and multidimensional magic angle spinning (MAS) NMR techniques at high magnetic fields, providing valuable structural information at the atomic-level about the fibril architecture. The secondary structures of both fibril types, determined by the assignment of similar to 80% of the backbone resonances of these 100- and 94-residue proteins,. respectively, reveal substantial backbone rearrangement compared with the location of beta-strands in their native immunoglobulin folds. The identification of seven beta-strands in h beta(2)m fibrils indicates that approximately 70 residues are in a beta-strand conformation in the fibril core. By contrast, nine beta-strands comprise the fibrils formed from Delta N6, indicating a more extensive core. The precise location and length of beta-strands in the two fibril forms also differ. The results indicate fibrils of Delta N6 and h beta(2)m have an extensive core architecture involving the majority of residues in the polypeptide sequence. The common elements of the backbone structure of the two proteins likely facilitates their ability to copolymerize during amyloid fibril assembly.