National Institute of Environmental Health Sciences researchers have invested considerable effort in exploring the utility of transgenic mice to detect carcinogens and study mechanisms of carcinogenesis. Work has assessed several mouse models genetically altered to enhance their expression of chemically induced tumors. Results with the p53def (hemizygous for the tumor-suppressor gene) and the Tg.AC (carrier of an activated H-ras oncogene) mice have been used as a basis for a proposed new strategy for identifying chemical carcinogens and assessing risk. The U.S. National Toxicology Program is conducting a series of studies with these two transgenic strains to further examine their strengths and weaknesses for identification of documented rodent and human carcinogens and to explore their ability to provide information concerning the effective dosimetry for target organ mutation.