The role of hepatic microsomal mixed-function oxidase metabolism of fluorinated ether anesthetics in potentiating the toxicity of the anesthetics will be investigated in rats. The hepatic cytochrome P-450 catalyzed metabolic pathways of a series of fluorinated ether anesthetics have been elucidated. In vivo studies relating blood concentrations of anesthetic metabolites to concentrations of the metabolites known to mediate toxic responses will be undertaken. The extent to which a variety of cytochrome P-450 inducing agents affect these concentrations of anesthetics will be determined and correlated with the effects of the inducing agents in potentiating anesthetic toxicity. Inducing agents which will be investigated are phenobarbital, pregnenolone-16 alpha-carbonitrile, and beta-naphthoflavone. Metabolites which will be investigated as the source of toxicity of the anesthetics are 2,2,2-trifluoroethanol and a series of aldehydes which arise from the nonfluorinated portions of the anesthetic molecules, and include acrolein. Complete necropsies of induced rats which are subsequently administered anesthetic will be performed and extensive histopathological examinations will be carried out to determine the site of tissue lesions. The effects of specific inhibitors of cytochrome P-450 in affecting blood concentrations of metabolites of subsequently administered anesthetics will also be investigated. The results of these investigations will be used to assess the role of cytochrome P-450 isozymes in potentiating the toxicity of fluorinated ether anesthetic compounds.