Experiments carried out in our laboratory during the past two years have established that diphenylcyclopropenone, 9-fluorenone, and chalcone oxide have pronounced effects upon those microsomal enzymatic activities involved in carcinogenic arylhydrocarbon metabolism. Each of these compounds has been found to be a stimulator of the in vitro activity of rat liver epoxide hydratase and an inhibitor of the in vitro activity of rat liver microsomal monooxygenase. It should be noted that (1) only a few compounds are known which act as in vitro stimulators of epoxide hydrastase activity, (2) these properties of diphenylcyclopropenone, 9-fluorenone, and chalcone oxide have not been previously observed, and (3) our preliminary data indicated that diphenylcyclopropenone and chalcone oxide are among the most active stimulators of epoxide hydratase yet reported. We propose to continue our investigations of these phenomena. I. Substituted diphenylcyclopropenones, 9-fluorenones, and chalcone oxides will be tested to determine the structure function relationships of these phenomena. II. Investigations will be carried out, including attempts to covalently label the activator and the catalytic sites of epoxide hydratase in order to determine the mechanisms responsible for the observed stimulation of epoxide hydratase activity. III. It will be determined if the pattern of hepatic metabolites produced from benzo(a)pyrene is altered by the presence of diphenylcyclopropenones, 9-fluorenones, or chalcone oxides in the assays medium, or by prior exposure of rats to these compounds plus 3-methylcholanthrene. Recent experimental results indicate that the ultimate carcinogenic forms of both benzo(a)pyrene and benz(a)anthracene are dihydrodiol oxide derivatives, formed by the sequential actions of microsomal monooxygenase and epoxide hydratase. Thus the carcinogenic activity of an arylhydrocarbon should depend upon the relative activities and specifities of these two enzymes. The proposed experimental studies may therefore indicate how anticarcinogens that would protect against arylhydrocarbon carcinogenesis might be developed.