Lines of hemopoietic progenitor cells can be grown for prolonged or indefinite periods in vitro in the presence of a specific growth factor produced by activated T lymphocytes, persisting (P)-cell-stimulating factor (PSF). From such a PSF-dependent line, we report the emergence of variants that had concomitantly acquired both the capacity for autonomous growth in the absence of exogenous PSF and the capacity for the autogenous production of PSF. The link between these two new properties was strengthened by the demonstration that the variant lines absorbed PSF and, in some culture conditions, responded to exogenous PSF. Thus when variant cells were plated at low density in 1-ml agar cultures, cloning efficiency and colony size were enhanced by supplementation with sources of PSF, including medium conditioned by concanavalin A-stimulated normal spleen cells, T-cell tumors and T-cell hybridomas, and, importantly, medium conditioned by the autonomous P-cell lines themselves. In contrast to the parental line, the autonomous clones tested formed progressively growing tumors in vivo. It is proposed that the myelomonocytic leukemia WEHI-3B that produces PSF arose from a neutrophil-macrophage progenitor through acquisition of the capacity for the autogenous production of PSF and that the autogenous production of PSF may play a similar role in a range of proliferative disorders both of the blood and of other tissues containing components derived from the bone marrow.