The purpose of this investigation is to study the natural history of lung cancer. Data collected through the National Cancer Institute's Cooperative Early Lung Cancer Detection Program will be analyzed to establish and quantitate the extent to which atypical squamous metaplasia (mild, moderate, and marked) predicts lung cancer development. 15,000 smokers free of lung cancer at the start of the study were followed for the development of the disease over a 12 year period. Sputum cytology specimens were collected every four months during a five year period. Information concerning potential confounding factors including age, race, occupational exposures to lung carcinogens, and smoking habits were obtained on questionnaires completed at the start of the study and at 4 month intervals. Poisson regression and proportional hazards modeling will be employed to determine whether degree of metaplastic atypia (particularly mild atypia) as detected by sputum cytology is associated with the risk of developing lung cancer, and whether changes in smoking habits (quitting or reducing consumption) affect progression and regression in degree of atypical metaplasia. Currently, the clinical significance of metaplastic atypias is uncertain, especially for mild atypias which are believed to be reversible. If degree of metaplastic atypia can be shown to be predictive of lung cancer development, a subset of smokers can be identified as having a higher than average risk of developing the disease. While smoking prevention and cessation are the primary strategies for the prevention of lung cancer, identification of smokers at particularly high risk could create new prevention opportunities by focusing antismoking efforts and enhancing motivation to quit smoking, and by providing target groups for screening and chemoprevention research.