Irreversible oxidative damage at both aromatic side chains and dipeptide linkage occurs in the aromatic N- and C-protected dipeptides 7-11 upon exposure to the environmental pollutants NO₂ and O₃. The reaction proceeds through initial oxidation of the aromatic ring by in situ generated NO₃, or by NO₂, respectively, which leads to formation of nitroaromatic products. The indole ring in Phe-Trp undergoes oxidative cyclization to a pyrroloindoline. An important reaction pathway for dipeptides with less oxidisable aromatic side chains proceeds through fragmentation of the peptide bond with concomitant acyl migration. This process is likely initiated by an ionic reaction of the amide nitrogen with the NO₂ dimer, N₂O₄. This journal is