It is well established that 1,25(OH)2D3 induces monocyte/macrophage (Mo/Mphi) colonies when added to culture of granulocyte/macrophage progenitors. Recently, we demonstrated that one of the target cells of 1,25(OH)2D3 in Mo/Mphi differentiation is the neutrophilic promyelocyte that is believed to belong to the neutrophilic lineage. This fact overthrows the established theory that normal hematopoietic precursors are committed to respective cell lineages and do not deviate from their own lineage. The lineage switching from the promyelocyte to Mo/Mphi was suggested to be operating in vivo because 1,25(OH)2D3 is a physiological substance produced by Mphi. More recently, we have shown that transient exposure (24 h) of promyelocytes to 1,25(OH)2D3 causes Mo/Mphi differentiation. This strategy could be useful for examining the effects of 1,25(OH)2D3 on the growth and differentiation of normal myeloblasts and myeloid progenitor cells. Recent advances in molecular biology have enabled investigators to identify a number of genes involved in Mo/Mphi differentiation induced by 1,25(OH)2D3. Some of these may be the determinant genes for Mo/Mphi differentiation; however, further studies are required to determine the underlying mechanisms of Mo/Mphi differentiation.