We have proposed that amyloid fibrils contain subunits (protofibrils) that are formed from beta-strands wound into continuous 2-3 nm-diameter beta-helices. Subsequent lateral aggregation of the beta-helices to form the widely observed 5-12 nm-diameter fibrils could be promoted by hydrophobic residues on the exterior of the postulated beta-helix. A number of short peptide fragments of the amyloid-beta (A beta) proteins, such as A beta34-42 [LMVGGVVIA], the nine-residue, carboxyl-terminal portion of A beta1-42, can also form amyloid fibrils. In the present study, it was found that a beta-helix formed from A beta34-42 accounts for features suggested by published rotational resonance solid-state NMR data, including an anomalous conformation about the Gly-37-Gly-38 region and exaggerated pleating. An analogue of A beta34-42 was synthesized in which the hydrophobic groups on the exterior of the postulated beta-helix were replaced with glutamates, giving LEVGGVEIE. The analogue was completely soluble at pH 7, but at pH 2.5 it produced 2-2.5 nm-diameter fibrils which did not associate into larger-diameter bundles. The results of this study support the proposal that amyloid fibrils are formed from beta-helical subunits.