A variety of transgenic mice, such as v-Ha-ras transgenic mice, pim-1 transgenic mice, mice carrying the human c-Ha-ras proto-oncogene, and mice deficient for tumor-suppressor gene p53, have been shown to exhibit increased carcinogen susceptibility. Therefore, studies designed to test the practical application of these animal models for use in medium-term screening of environmental carcinogens have been conducted. As test animals, however, rats have several advantages over mice: larger organ size, abundant information regarding characteristics of preneoplasias, and virus-free constitution. We have generated transgenic rats bearing the human c-Ha-ras proto-oncogene (strain Hras128) and shown that the females are highly susceptible to chemically-induced mammary carcinogenesis, and males, to a lesser extent, urinary bladder, oesophagus and skin carcinogenesis. The tumors which develop in these animals’ exhibit mutations in the ras gene, and in most of these tumors the ras gene mutations were found exclusively in the transgene and not in the endogenous gene. These mutations appeared to occur early in the process of carcinogenesis, which involves proliferation of cells in terminal end buds (TEBs) and intraductal hyperplasia before carcinomas develop. Based on our findings of high susceptibility to N-methyl-N-nitrosourea (MNU), dimethylbenzo[a]anthracene (DMBA), and 2-amino-1-methl-6-phenylimidazo[4,5-b]pyridine (PhIP) in inducing mammary carcinomas in a short time (6–12 weeks), we examined various known carcinogens which do not normally induce mammary carcinomas using famale Hras128 rats. Significant increases in mammary carcinomas was observed in groups administered 3-MC, B[a]P, anthracene, IQ, MeIQx, and azoxymethane (AOM). With 3-MC, B[a]P, IQ, and AOM, mutations of the transgene in codons 12 and 61 were observed in the induced carcinomas. Thus various carcinogens, not necessarily limited to those normally targeting the mammary gland, were found to induce mammary carcinomas, pointing to the potential use of c-Ha-ras transgenic rats for use in medium-term screening.