Our research efforts are directed toward investigating both the means of induction and the morphogenesis of cancer in the major airways of the respiratory tract. The model employed has been the heterotopic tracheal transplant which allows for quantitative exposure of circumscribed segments of rodent tracheal epithelium to chemicals and particulates of known or suspected carcinogenicity. Studies of changes in tracheal epithelium induced by known carcinogens suggest that cancers develop from certain focal lesions which arise long after cessation of carcinogen exposure. Studies with nickel and asbestos have demonstrated that both are irritant substances but have at most low carcinogenicity for tracheal epithelium. We are also in the process of (1) comparing the effect of the length of exposure to carcinogens vs. the total delivered dose through modification of the delivery system and (2) assessing the susceptibility of tracheal tissue from aged animals to chemical carcinogens. We are also assessing the applicability of the phenomena of promotion and co-carcinogenesis to the respiratory tract.