12-O-Tetradecanoylphorbol-13-acetate (TPA), a potent promoter of mouse skin carcinogenesis, was tested for possible tumor-enhancing effects on urinary bladder carcinogenesis using the heterotopically transplanted bladder (HTB) model. Weekly administration of TPA at 1.0 microgram/week to N-methyl-N-nitrosourea-initiated HTBs did not increase tumor incidence, but instead, resulted in a significantly high incidence of nodulopapillary hyperplasia, an early neoplastic lesion, suggesting possible tumor enhancement by TPA. In addition, administration of a high dose of TPA with or without a carcinogen treatment led to the development of numerous finger-like epithelial projections on the luminal surface of the HTBs. Evidence indicates that epithelial projections are formed as a result of proliferation of intermediate cells. Whether these structures evolve into true neoplastic lesions is at present unknown.