We report that sodium butyrate, a natural product of fiber degradation by colonic bacteria, markedly suppresses c-Myc-mediated apoptosis induced in murine plasmacytomas and human Burkitt lymphomas by growth factor deprivation, but not in cell lines devoid of c-myc translocations. Attenuation of cell death is associated with downregulation of the rearranged c-myc and activation of pRb via its dephosphorylation. We suggest that in vivo sodium butyrate may play an important role in plasmacytomagenesis by supporting the survival of cells with c-myc translocations, which otherwise would be eliminated by the lack of growth factors.