Methionine in glycine-rich regions of both beta -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)(2)SH+ 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)(2)S 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 C-alpha-H site of almost any amino acid residue of a nearby polypeptide strand (BDE(C-alpha-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 beta -sheet, only a Gly residue is exposed and susceptible to oxidation at the C-alpha-H site. Furthermore, the Gly must lie on a strand of the beta -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 A beta 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 beta -sheets and amino acids, methionine and glycine.