Abstract The genomes of MH2 and MC29 have been shown to be highly similar and contain the same oncogenic sequence termed myc. Both viruses can transform Japanese quail ( Coturnix coturnix japonica) embryo fibroblasts and mature peripheral blood macrophages in vitro. However, a striking difference is observed after in vivo infection of 3-week-old quail. Neither virus causes either sarcomas or myelocytomas. MC29 is only weakly oncogenic; only two of 29 birds developed tumors which were localized in the liver. In contrast MH2 is highly oncogenic; birds generally developed solid tumors near the site of injection, or liver tumors. When the solid tumors were placed in culture they gave rise to transformed macrophages, and surprisingly, erythrocyte-like cells, which were not transformed. MH2 and MC29 also exhibited different efficiences of macrophage and fibroblast transformation in vitro. It is postulated that the biological differences between the two viruses could be related to differences in processing of myc sequences.