Transgene expression and skin tumorigenicity were investigated in transgenic TG-AC mice carrying the v-Ha-ras after treatment with benzo[a]pyrene (BP). Animals treated with 40 microg BP (x2/week/mouse) showed 100% tumor response after 25 weeks, as did 40% of the mice treated with 20 microg BP but 10 microg BP did not produce a tumor response. In the case of animals treated with 40 microg BP for 25 weeks, most of the tumors were proven to be carcinomas (80%, 4 out of 5 mice), and all tumors were shown to be positive in terms of transgene expression detected by in situ hybridization. These data suggest that BP was tumorigenic in a dose-dependent manner in TG-AC mice and that TG-AC mice were dependent on transgene expression during BP carcinogenesis.