. This is a resubmission of a application reviewed at the October 1996 meeting of the EDC-2 Study Section. A detailed response to the comments by the previous reviewers is included. The application has been considerably revised and re-written. Field cancerization is defined as resulting throughout the respiratory tract because of a broad exposure to carcinogens. Thus, cells throughout the airways will develop genetic abnormalities, regardless of whether they develop malignant change. Important to the overall goals is the postulate that genetic abnormalities in these non-malignant bronchial epithelial cells show a strong association for the development of lung cancer. This will be tested by a hospital-based, case-control study, comparing age, gender and smoking matched (essentially all will be smokers or ex-smokers and all will be men) patients with and without lung cancer. Nonmalignant bronchial epithelial cells will be obtained by bronchoscopy and analyzed by fluorescence in situ hybridization and immunohistochemical techniques in order to determine which among the five alterations most common in lung tumors (expression of p53, loss of chromosome fragments at 9p21, 3p21, 17p13, and trisomy 7) show the strongest correlations with this disease. These results will determine whether genetic alterations detected in nonmalignant bronchial cells are markers for respiratory carcinogenesis (c.f., simply markers of exposure) and help identify genetic alterations that are candidate markers of respiratory carcinogenesis.