Methionine, cysteine and cystine, which were acetylated at the N-terminus and methylated at the C-terminus, react rapidly with the environmental nitrate radical (NO3.) with rate coefficients of 7.7×109, 3.4×109 and 2.0×109 M−1 s−1, respectively, in acetonitrile. Methionine (Ac−Met−OMe) is successively oxidized via the sulfoxide (Ac−MetO−Me) to the sulfone (Ac−MetO2−OMe), with the latter step being also extremely fast with a rate coefficient of 1.2×109 M−1 s−1. Computations predict formation of an initial charge transfer complex between NO3. and the S or SO moiety in Ac-Met-OMe, Ac-MetO-OMe and cystine (Ac−Cys(S−S)Cys-OMe), respectively, which is followed by simultaneous S−O bond formation and NO2. expulsion. Calculations for the reaction of cysteine (Ac-Cys-OMe) with NO3. revealed side-chain oxidation to give a thiyl radical or a sulfenic acid as likely pathways. These findings highlight the potential harmful impact of NO2./O3 pollution on S-containing amino acid residues in peptides.