Inoculation of tumorigenic prostatic stroma and nontumorigenic prostatic epithelia into the subcutaneous space of syngeneic rats induced the development of carcinosarcoma. The induced tumors, which were composed of a mixture of adenocarcinoma and fibrosarcoma, were androgen responsive. This model offers a novel mechanism for prostatic carcinogenesis in which prostatic fibroblasts determine epithelial growth, androgen responsiveness, and tumorigenicity. Our results emphasize the potential importance of an epigenetic pathway in prostatic carcinogenesis.