Many alpha,beta-unsaturated compounds are sufficiently reactive to condense with nucleophiles under physiological conditions and are potentially deleterious to cellular processes. These compounds react with thiols by nucleophilic attack to give 1,4 addition products. We have examined the products formed from the reaction of the model thiols HSCH2CH2OH and glutathione with methylvinylmaleimide, a Michael acceptor with extended conjugation. Glutathione produced exclusively a 1,6 addition product with methylvinylmaleimide. HSCH2CH2OH also formed a 1,6 nucleophilic addition product, as well as a disubstituted product resulting from apparent further 1,4 addition to the 1,6 addition product. Two other novel products which resulted from addition to the maleimide ring and addition at the vinyl carbon proximal to the maleimide ring were observed.