High-resolution structures of oligomers formed by the beta-amyloid peptide A beta are needed to understand the molecular basis of Alzheimer's disease and develop therapies. This paper presents the X-ray crystallographic structures of oligomers formed by a 20-residue peptide segment derived from A beta. The development of a peptide in which A beta(17)_(36) is stabilized as a beta-hairpin is described, and the X-ray crystallographic structures of oligomers it forms are reported. Two covalent constraints act in tandem to stabilize the A beta(17)_(36) peptide in a hairpin conformation: a delta-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29. An N-methyl group at position 33 blocks uncontrolled aggregation. The peptide readily crystallizes as a folded beta-hairpin, which assembles hierarchically in the crystal lattice. Three beta-hairpin monomers assemble to form a triangular trimer, four trimers assemble in a tetrahedral arrangement to form a dodecamer, and five dodecamers pack together to form an annular pore. This hierarchical assembly provides a model, in which full-length A beta transitions from an unfolded monomer to a folded beta-hairpin, which assembles to form oligomers that further pack to form an annular pore. This model may provide a better understanding of the molecular basis of Alzheimer's disease at atomic resolution.