The highly leukemogenic avian retrovirus E26 contains two oncogenes, v-Myb and v-Ets, which are expressed together as a fusion protein. The cellular homolog of v-Myb, designated c-Myb, encodes a transcription factor. Deletion or disruption of a negative regulatory domain mapping within the carboxy-terminal domain of c-Myb results in enhanced transactivating capacity and in parallel, leads to activation of its ability to transform hemopoietic cells. c-Myb is expressed preferentially, but not exclusively, in immature hemopoietic cells and its expression decreases as cells differentiate.