There is a growing body of basic science and epidemiologic evidence to support a research thrust to determine whether several natural or synthetic agents, given alone or together, can lower cancer incidence. Candidate agents include analogs of vitamin A and the vitamin A precursor, beta-carotene, vitamins C and E, and the trace metal selenium. Other agents now being studied in the laboratory include phenolic antioxidants, protease inhibitors, prostaglandin synthesis inhibitors, and indoles. Research in chemoprevention involves identifying and characterizing agents with reported activity, efficacy and toxicologic testing to select the most promising agents, and clinical trials to test those with the most potential in humans. Activities are underway in all the above areas, including 24 clinical trials, to evaluate selected compounds in preventing cancer at various cancer sites. Included are studies of individuals at high risk, individuals with precancerous lesions and individuals free of cancer but at risk to second cancers. A number of agents have shown activity in reducing bladder cancer incidence in animal models. The potential applicability of these agents for studies in human cancer risk reduction intervention studies is discussed. Cancer induction is postulated to be a multistage process involving initiation and promotion. Progress in cancer prevention may result from not only reducing exposures to initiators, but also suppressing promotional activity in initiated cells. Newly developed research technologies including cellular, animal, and epidemiologic procedures are being used for identifying, refining, and testing cancer prevention strategies.