Many industrially and environmentally used chemicals contain a chloro-olefin group or are metabolized via chloro-olefins. Many of these chloro-olefins have been shown to be carcinogenic and/or mutagenic due to their metabolism to a reactive alpha-chloro-epoxide electrophile. We sought to determne if the carcinogenicity of DDT and that of two of its major metabolic products, DDE and DDD, is mediated by an analogous formation of an alpha-chloroepoxide. Our studies show that DDMU, a metabolite formed from DDT, DDE and DDD, is converted to the corresponding epoxide in vivo and that this epoxide is mutagenic in the Ames system. We are also studying the reaction of a series of chloroepoxides, in terms of their rate of hydrolysis and thermal isomerization. The purpose of this work is to better understand the metabolism of chloro-olefins and the reaction of their corresponding epoxide metabolites with cellular macromolecules.