The pathogenesis of signal morphological lesions of the urinary bladder induced in several species following administration of N-butyl-N-(4-hydroxybutyl)nitrosamine, bracken fern, or N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide is presented. Incidences of bladder neoplasia exceeding 80% were generated in the rat by each compound. Bladder neoplasia was induced in the following species by each substance: by N-butyl-N-(4-hydroxybutyl)nitrosamine in the mouse, hamster, guinea pig, and dog; by bracken fern in the guinea pig, mouse, and cow; and by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide in mouse, hamster, and dog. The guinea pig appeared resistant to the bladder oncogenicity of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide. Different species displayed a gradient of bladder neoplastic responsiveness. Hyperplasia was a consistent early lesion and was usually focal. Early hyperplastic lesions regressed following removal of the carcinogenic stimulus, but later lesions appeared to be irreversible. These animal systems appear useful in providing opportunities for investigations relevant to human bladder cancer.