Sharpening the focus of possible cancer prevention programs is likely to require the identification of risk factors that are related as closely as possible to exposures and reactions at the cellular level. Ascertaining serologic precursors of cancer is one step in this direction. The major source of serum for this study came from a program in 1974 in Washington County, Maryland, in which nearly 26,000 persons each donated 15 ml of blood. The serum has been kept frozen at -73 C since that time. Cancer cases developing among the serum donors have been identified by the Washington County cancer registry in our center. By November 1985, it is estimated that 1142 donors will have developed cancer. Among the 931 persons with cancers at one of the 17 sites with at least 10 cases and two controls for each case, serum will be analyzed for vitamins A and E, carotenoids and selenium, all of which are antioxidants suspected of inhibiting carcinogenic changes among cells. Cholesterol levels will also be determined because of the association of this serum component with serum levels of vitamins A and E. Serum from cervical and prostatic cancer cases and their controls will be be examined for antibodies against herpes-2 virus. Cytomegalovitus antibodies will be determined among prostatic cancer cases and controls, as well as serum zinc and testosterone, prolactin, luteinizing hormone, sex hormone binding globulin, and thyroid stimulating hormone. In addition to comparisons of levels of these nutritional, antibody, and hormonal factors among cases and controls, comparisons will also be made of the serum levels before and after the diagnosis of cancer. Possible interactions will be sought between the nutritional factors of all cancers and their controls, and among prostatic cancer cases and controls, between the hormonal factors.