The oncogene v-erb-B has been shown to transform pre-B lymphocytes and early erythroid precursor cells and has been implicated in leukemogenesis. We have examined the effect of this oncogene on the growth of a murine myeloid interleukin-3 (IL-3)-dependent cell line, FDC-P1, FDC-P1 cells were infected with a recombinant murine retrovirus containing v-erb-B. As a result, clonal IL-3-independent cell lines (FI-v-erb-B) were generated with a high level of v-erb-B expression and an altered morphology compared to parental FDC-PI cells. The F1-v-erb-B cells were tumorigenic and did not express or secrete IL-3, suggesting the acquisition of IL-3 independence by a non-autocrine mechanism. In addition to the formation of myeloid colonies, FI-v-erb-B cells, when grown in semi-solid medium with exogenous IL-3, erythropoietin (Epo), or IL-3 plus Epo, could also form erythroid and mixed-erythroid colonies. By contrast, parental FDC-P1 cells formed only myeloid colonies under the same conditions. Our results indicate that v-erb-B abrogates growth factor dependence in these cells and may cause lineage modulation by acting to allow the induction of erythroid differentiation in FI-v-erb-B cells.