THE putative oncogene bcl-2 is juxtaposed to the immunoglobulin heavy chain (Igh) locus^1-3 by the t(14;18) chromosomal translocation typical of human follicular B-cell lymphomas⁴. The bcl-2 gene product (refs 5,6) is not altered by the translocation, but its expression is deregulated^6–8, presumably by the Igh enhancer Eµ. Constitutive bcl-2 expression seems to augment cell survival, as infection with a bcl-2 retrovirus enables certain growth factor-dependent mouse cell lines to maintain viability when deprived of factor^9,10. Furthermore, high levels of the bcl-2 product can protect human B and T lymphoblasts under stress^11,12 and thereby confer a growth advantage^12–14. Mice expressing a bcl-2 transgene controlled by the Igh enhancer accumulate small non-cycling B cells which survive unusually well in vitro^15–17 but do not show a propensity for spontaneous tumorigenesis^15,16. In contrast, an analogous myc transgene, designed to mimic the myc–Igh translocation product typical of Burkitt's lymphoma and rodent plasmacytoma¹⁸, promotes B lymphoid cell proliferation and predisposes mice to malignancy in pre-B and B lymphoid cells^19-22. Previous experiments have suggested that bcl-2 can cooperate with deregulated myc to improve in vitro growth of pre-B and B cells^9,11. Here we describe a marked synergy between bcl-2 and myc in doubly transgenic mice. Eµ–bcl–2/myc mice show hyperproliferation of pre-B and B cells and develop tumours much faster than Eµ–myc mice. Surprisingly, the tumours derive from a cell with the hallmarks of a primitive haemopoietic cell, perhaps a lymphoid-committed stem cell.