Methionine in glycine-rich regions of both β-amyloid peptide and prion peptide is thought to be crucial to their neurotoxic properties. We postulate here a role for methionine in the propagation of oxidative damage. The S−H bond dissociation enthalpies, BDE(S−H)s, of dimethylsulfonium ion (CH3)2SH+ and a S-protonated methionine residue of a polypeptide strand are estimated to be 351 and 326−331 kJ mol-1, respectively, by the application of calculations at the B3LYP level with large basis sets. These species are direct products of H atom abstraction by radical cations of sulfides. The reactions between a glycine residue and the radical cations of (CH3)2S and Met were investigated and the transition structures for H atom transfer located. The results suggest that it is thermodynamically feasible for the S-ionized form of Met to cause oxidative damage at the αC−H site of almost any amino acid residue of a nearby polypeptide strand (BDE(αC−H) = 330−360 kJ mol-1) or to nearby lipids with a bis(allylic) methylene group (BDE(C−H) = 335 kJ mol-1). However, a key observation is that, when the Met residue is incorporated into an antiparallel β-sheet, only a Gly residue is exposed and susceptible to oxidation at the αC−H site. Furthermore, the Gly must lie on a strand of the β-sheet different from that containing Met and must be part of a (5,5) rather than a (3,3) cycle. The same considerations apply to the methyl-deprotonated form of the sulfide radical cation but not the methylene-deprotonated form. These findings suggest a possible mechanism for generating and propagating oxidative damage via a Met residue of the Aβ peptide of Alzheimer's disease and of the prion peptide of Creutzfeldt−Jakob disease. To our knowledge, this is the first proposed mechanism that accounts for the radical damage in either of these diseases and requires peptide β-sheets and amino acids, methionine and glycine.