Three-methylindole (MI) causes acute pulmonary lesions in cattle, goats, and sheep during the course of its metabolism by the mixed function oxidase system. We plan to investigate the mechanism of pulmonary toxicity and identify the lung toxic metabolite(s). These experiments will involve in-vitro microsomal metabolism studies to determine the reactions responsible for the formation of reactive intermediates. We plan to conduct in-vivo studies to verify in-vitro observations related to the mechanism of pulmonary toxicity. Emphasis will be placed on elucidation of metabolic pathways and enzymes associated with the disposition of 3MI in different tissues and species. In addition, we plan to evaluate fermentation conditions which affect the growth and fermentation potential of the bacteria which produce 3MI in anaerobic systems. This information will be used to devise an effective means of inhibiting the formation of 3MI which should lead to the prevention of acute pulmonary edema in animals. A long term goal is to assess the risk of exposure to 3MI in man.