The ability to induce neoplasia in lower animals has been the basis for our understanding of the pathogenesis of neoplasia. Early studies showing the induction of skin cancer in mice by coal tar derivatives and of liver cancer by organic dyes (Chapter 3) led to the establishment of model systems in these and other tissues, both for the investigation of cancer development and ulti- mately for testing of agents for their carcinogenic potential. The administration of chemicals in the diet for extended periods, pioneered in the 1930s by Yoshida and colleagues (Sasaki and Yoshida, 1935), formed the basis for the establishment of the chronic bioassay of carcinogenic- ity that is used today. This methodology was espoused by the National Cancer Institute some 30 years after Yoshida’s findings (Hadidian et al., 1968), and almost 200 assays of chemicals for their carcinogenic potential by the prolonged feeding to animals was carried out over the next decade (Hottendorf and Pachter, 1985). Parallel to the use of this lifetime model of carcinogene- sis in small rodents was the development of various organ-specific model systems, multistage models, and most recently the use of transgenic animals in carcinogen testing. A listing of these animal models is seen in Table 13.4.