The effects of TPA, PDD, PDB, PDA, or MEZ on epithelial and mesenchymal skin tumors induced by a s.c. injection of MCA were studied histologically. Group-I mice received only MCA. At 6 weeks after MCA injection, mice in groups II to VII received acetone, 1.8 nmol TPA, PDD, PDB, PDA, or 6.1 nmol MEZ respectively in 0.1 ml acetone twice weekly until tumor development. Alterations in skin tumor induction patterns were also studied in animals that had been exposed to TPA or acetone for 10 weeks prior to s.c. injection of MCA. Exposure of mouse skin to TPA before or after carcinogen administration increased 2- to 3.5-fold, the incidence of carcinoma and mixed tumors of epithelial and mesenchymal histogenesis. The average time of tumor induction decreased in mice treated with MCA + TPA and 100% of the test animals in the TPA + MCA group developed tumors. In contrast, TPA-related phorbol esters inhibited skin tumor development, particularly trichoepithelioma and fibrosarcoma and increased the average time of tumor induction.