B cell stimulatory factor-1 (BSF-1)/Interleukin 4 (IL 4) is a T cell product originally characterized on the basis of its actions on B lymphocytes. Recently it has been reported that BSF-1 activates T cell and mast cell lines. We now provide evidence that BSF-1, purified to homogeneity, also has a broad spectrum of activity on hematopoietic progenitor cells (HPC). However, like its action on B cells, prolierative effects were only observed when BSF-1 was combined with an additional factor. Thus BSF-1, in costimulation with recombinant G-CSF, enhances the proliferation of granulocyte-macrophage progenitor cells (CFU-GM). BSF-1 increases the proliferation of CFU-e in the presence of recombinant erythropoietin (rEPO). Furthermore, BSF-1 induces, together with rEPO, colony formation by primitive erythroid (BFU-e) and multipotent (CFU-mix) progenitor cells comparable to that observed with rEPO and interleukin 3 (IL 3). BSF-1 is also active as a megakaryocyte colony-stimulating factor; in combination with recombinant interleukin 1, rEPO or the supernatant of the T cell hybridoma FS7–20.6.18, BSF-1 induces megakaryocyte colony formation (CFU-Mk). The same factors that synergize with BSF-1 also enhance CFU-Mk proliferation induced by IL 3. Although the precise mechanisms of action of BSF-1 on HPC is not yet known, we propose that BSF-1 represents an activation factor for HPC and prepares the progenitor cells to respond to specific growth or differentiation factors.