Emu-myc transgenic mice constitutively express the c-myc oncogene from before birth, but their inexorable development of B-lymphoid tumors appears to require rare spontaneous alterations within B-lineage cells. To determine whether other oncogenes can cooperate with myc to induce B-lymphoid transformation, we infected neonatal Emu-myc mice and normal littermates with helper-free retroviruses bearing the v-H-ras, v-raf, or v-abl oncogene. The v-H-ras and the v-raf oncogene dramatically accelerated Emu-myc pre-B-lymphoma onset, whereas v-abl did not, despite the increased numbers of presumptive target pre-B cells in Emu-myc mice. These results imply that v-H-ras and v-raf synergize with deregulated myc expression to transform pre-B cells, while v-abl apparently does not.