The metabolism and binding of the volatile carcinogen 1,2-dibromo[14C]ethane (DBE) were studied in C57BL mice, Sprague-Dawley rats, and Fischer rats. As shown by the wholebody and light microscopic autoradiography with heated and/or extracted sections, a selective accumulation of metabolites occurred in a number of tissues, preferentially in the reported target tissues for DBE-induced lesions [i.e., in the nasal cavity, lung, forestomach, and liver (tumors) and the adrenal, testicle, liver, and kidney (nonneoplastic lesions)]. High levels of nonextractable metabolites were registered in the epithelia of the entire respiratory tract, the upper alimentary tract, the vagina, and the subepithelial glands of the olfactory mucosa. Lower levels of metabolites were observed in the liver, adrenal cortex, testicular interstitium, and kidney. Autoradiography of slices from various extrahepatic tissues incubated in vitro with DBE showed that most epithelia of the respiratory tract, upper alimentary tract, vagina, and the testicular interstitium have a marked ability to activate DBE to metabolites that become bound to the tissue. Further in vitro experiments, performed with S-1 fractions prepared from various tissues, indicated that the nasal mucosa was most active in transforming DBE to products which could not be extracted from the protein precipitate. It is proposed that tissue-selective metabolism and activation of DBE in the epithelia of the respiratory and upper alimentary tract are responsible for the observed DBE-induced lesions in these organ systems.