The specificity of murine leukemia virus-induced myelomonocytic phenotypic changes in long-term bone marrow culture have been examined by comparing the effects of polycythemia-inducing Friend leukemia virus (FVP) and Moloney murine leukemia virus (M-MuLV) known to have in vivo target cells in the erythroid and lymphoid lineage, respectively. Noninfected adn M-MuLV-infected cultures showed no modification in granulocyte macrophage colony-forming cell behavior and failed to generate cell line in WEHI-3-conditioned medium. In contrast, in FVP-infected cultures, granulocyte macrophage colony-forming cells became colony-stimulating factor independent, and the nonadherent cells gave rise to two cell lines in WEHI-3 conditioned medium with monocytic characteristics and no leukemogenic potential in vivo. These results confirm the ability of long-term bone marrow culture to unmask target cells for FVP within myelomonocytic progenitors, and the negative results in M-MuLV-infected cultures underline the specificity of the FVP-induced phenotypic changes. Despite a high level of virus production and the presence of T-cell precursors in the M-MuLV infected culture, T-cell transformation was not observed.