The Ets family transcription factor PU.1 is required for development of various lymphoid and myeloid cell lineages, and regulates the expression of several genes in a cell type-specific manner. Mouse bone marrow-derived hematopoietic progenitor cells are programmed to differentiate into mast cells, when the cells are maintained in the presence of pokeweed mitogen-stimulated spleen-conditioned medium. However, by retroviral introduction of PU.1 cDNA, the progenitor cells expressed MHC class II, CD11b, CD11c, and F4/80, and acquired the ability to stimulate T cells. Furthermore, PU.1-overproducing cells exhibited the morphology, in part, similar to that of monocyte. These results indicate that the mast cell progenitors still have the ability to express monocyte-specific genes by increased expression of PU.1.