Bladder neoplasms that are morphologically similar to those occurring in the human bladder can be induced in rats and mice. Thus, these animal models can provide useful information in elucidating the histogenesis of the human bladder cancer. It is unknown whether human and rodent bladder cancers share similar molecular mechanism(s). There are species-specific differences in the type of neoplastic lesions. In rats, irrespective of the carcinogen used, the lesions tend to be polypoid exophytic masses and invasion is a late event, occurring only after a large dose of carcinogen and after an extended period of observation. On the other hand, mice tend to develop nodular invasive carcinomas readily preceded by the development of CIS. In both species, the neoplasms tend to show squamous differentiation, and metastatic spread is rare. Nevertheless, both species provide a useful model for the assessment of human risk of test chemicals because the principal neoplastic lesions that develop in response to test carcinogens are transitional cell neoplasms. Further study of cases of chemically, induced bladder cancer in rodents is essential to determine the applicability of the mode of action to humans.