Although exposure to tobacco smoke is now recognized as the major risk factor for lung cancer; the fact that many smokers do not develop the disease suggests that other factors must be involved. Among the possible protective agents are the antioxidant micronutrients, especially the carotenoids, tocopherols, ascorbic acid, and selenium. The last is a marker for the antioxidant enzyme, glutathione peroxidase. Only a few of these substances, namely beta-carotene, alpha-tocopherol and selenium, have been studied in more than one or two populations. Associations of the other studies are needed to indicate whether controlled trials of these substances are desirable. Almost nothing is known about associations of antioxidant nutrients with lung cancer by gender, and little about their associations by smoking history or by cell type. This information could be important for understanding pathogenesis and for prevention. The proposed study will have a nested case-control design, assaying serum collected in 1974 and 1989 for serum levels of various antioxidant nutrients among the estimated 300 persons who will have developed lung cancer after donating blood in 1974 or 1989 with 600 matched controls who have not developed lung cancer. Analyses will be done for the total study population, and separately by gender, smoking status, and cell type. The findings will add new knowledge about several antioxidant nutrients that have not yet been studied in this context and which could be useful in preventive programs. The results will also give the first solid information about antioxidant nutrients in serum and lung cancer in women.