The proto-oncogene c-fos has been isolated as the cellular homolog of the v-fos gene found in the osteosarcoma inducing FBR- and FBJ-murine sarcoma viruses (MSV). Expression of the c-fos gene in transgenic mice leads to the development of bone lesions of which about half progress to bone tumors mainly chondrosarcomas. The tumors display a strong preference for males and have a latency with a mean of 9.5 months. However, also mice without visible lesions develop bone tumors with the same sex preference and latency. These consequences of c-fos expression are independent of the chosen promoter but dependent on a replacement of 3' noncoding sequences of c-fos by a long terminal repeat (LTR) of the FBJ-MSV virus.