|Conversion of methionine to methionine sulfoxide can take place during postranslational modification, formulation, storage or synthesis of proteins. Therefore, methionine sulfoxidation is a major concern to pharmaceutical industries. Small model peptides containing methionine were oxidized by mercaptoethanol/FeCl, system in phosphate buffer. These studies were carried out to investigate the factors affecting methionine oxidation and the mechanism involved in the sulfoxidation. The effect of pH, buffer concentration, Fe(III) concentration, type of thiol, mercaptoethanol concentration and EDTA concentration on the formation of methionine sulfoxide was examined. The model peptides studied included His-Met, Met-His, Gly-Met, Gly- Met-Gly, Gly-Gly-Met and Met-Gly-Gly. The initial rate of formation of methionine sulfoxide was observed to be dependant on the iron concentration and thiol concentration. However, the initial rate of formation of methionine sulfoxide was independent of the phosphate buffer concentration. The presence of EDTA not only suppressed the formation of sulfoxide but also caused an increase in peptide degradation. The influence of the location of methionine on the yield of sulfoxide was also investigated. Maximum sulfoxide formation was observed when methionine was in the carboxyl-terminal position in the peptide, His-Met. The possible role of various reactive oxygen species was studied by using various trapping agents. The involvement of freely diffusible hydrogen peroxide, superoxide, and OH. in this oxidation process was found to be negligible. It may be also possible that these reactive oxygen species may not be involved in the rate determining step. However, the presence of bound reactive oxygen species cannot be ruled out, as these may not be trapped by the trapping agents used in this study. These studies and future elucidation of the chemical mechanisms involved in methionine sulfoxidation will provide a better understanding of the susceptibility of various proteins and peptides to degradation.