Cancer chemoprevention research takes leads from epidemiologic and laboratory research and develops them through in vitro and in vivo preclinical research and initial human studies into randomized controlled clinical trials. At present, the chemoprevention program is sponsoring 21 human efficacy studies. These trials are testing the potential of agents (beta-carotene, folic acid, 13-cis retinoic acid, 4-hydroxyphenyl retinamide, vitamins C and E, and minerals) as inhibitors of a variety of cancers in humans (colon, lung, esophagus, cervix, bladder, and skin). Endpoints in these studies include overall incidence of cancer, incidence of specific cancers, rate of regression or progression of preneoplastic changes, and changes in cellular or biochemical parameters. Study participants include volunteers from the general population; populations at high risk for cancer because of occupation, lifestyle, or place of residence; persons with previously treated cancers; and persons with preneoplastic lesions. Study designs include single agent randomization, combination of agents and complete factorial designs.