A proposed epidemiologic study for investigating possible mechanisms of lung cancer in persons occupationally exposed to crystalline silica (14808607) was discussed. The general goal of the study was to reconcile discrepancies between the results of epidemiologic and experimental animal studies. The epidemiologic studies have produced conflicting or equivocal results, whereas the animal studies have shown silica dust to be carcinogenic. The specific goals of the study were to test two hypotheses: that inhaled silica or parenchymal silicosis induces proliferation of pulmonary epithelial cells, thereby increasing the risk of lung cancer, and that silicosis of hilar lymph nodes impedes clearance of known carcinogens, thus increasing their residence time. The study material consisted of an autopsy archive of lung tissue specimens from a large number of former uranium miners who had been employed in underground mines in Saxony and Thuringia in the former German Democratic Republic after World War-II. The archive is considered to be unique in that it contains a large number of cases due to the high autopsy rate and the availability of detailed work histories and industrial hygiene data. In the uranium mines, the workers had been exposed to a wide range of radon (10043922) doses as well as silica from the mine dust. The autopsy archive consists of approximately 1.5 million histologic slides and 35,000 autopsies covering the period 1957 to 1992. Approximately 5,000 of the autopsies are from underground uranium miners who reportedly died of lung cancer. The response variables of the study that will be analyzed will be based on pathologic evaluations and will include tumor location, histologic type of lung cancer as determined according to the World Health Organization classification system, the presence and type of premalignant precursors, and the presence, extent, and specific sites of silicosis. The procedures to be used in the study are being evaluated by sampling 250 autopsy cases based on year of birth, year of death, type of employment in uranium mining, gender, and pathological diagnosis in a pilot study.