Since it was shown (2) that the treatment of casein with ethylene oxide could diminish the biological availability of the histidine and methionine of this protein, it became of interest to determine whether other proteins were affected in the same way and to elucidate the nature of the chemical reactions involved. Particular interest in such reactions derives from the use of ethylene oxide as a fumigant in the food industry (3,4) and from the inability of an earlier study (5) of proteins treated with this reagent to account for the interaction with histidine and methionine. The reactions of ethylene oxide with available sulfhydryl, hydroxyl, carboxyl, and primary amino groups of proteins have been documented (5). The destructive action of ethylene oxide on histidine and methionine has now been observed with two other proteins, and ethylene oxide. Chemical justification for these observations was sought. Initially, model systems were investigated in which the individual amino acids of amino acid derivations were treated with ethylene oxide in aqueous solution. In the case of histidine, the studies have been extended to intact protein. Evidence is presentation that the nitrogen atoms of the imidaxole ring and the sulfur of methionine undergo hydroxyethylation under mild conditions in the presence of ethylene oxide, imidazole yielding the 1,3-bis-(2-hydroxyethyl)imidaolium ion and N-acetyl-methionine being converted to S-(2-hydryoxyethyl-N-acetyl-methionine, thetin. The double alkylation of the mercapto group of cystein also can result in formation of sulfonium derivative.