A retroviral expression vector carrying the c-erbB-2 gene was introduced into the FDC-P2 myeloid cell line, which is absolutely dependent on interleukin-3 (IL-3) for proliferation and survival. Since the c-erbB-2 protein appears to be the receptor of an as yet unidentified growth factor, epidermal growth factor receptor (EGFR) was used as a control of a ligand-dependent receptor. FDC-P2 cells expressing normal c-erbB-2 were unable to grow without IL-3 stimulation. The c-erbB-2 protein in these cells was under-phosphorylated on tyrosine residues in vivo. On the contrary, the active c-erbB-2 protein, in which Val-659 was replaced by Glu in the transmembrane domain, and EGF-stimulated EGFR showed significant levels of tyrosine phosphorylation in vivo. These active proteins could promote short-term growth of FDC-P2 cells without IL-3 stimulation, though not indefinitely. These findings suggested that immortalization of this factor-dependent cell line requires an additional oncogenic promoting process(es).