We have isoiated cDNA clones of myelold differentiation primary response (MyD) genes, activated in the absence of de novo protein synthesis following induction for differentiation along elther the macrophage or granulocyte lineage in human myelobiastic leukemia HL-99 cells. One cDNA clone of a primary response gene, expressed upon macrophagedifferentiation, encoded for Egr-1, a zinc finger transcription factor. The Egr-1 gene was observed to be transcrlptlonally silent in HL-99 cells, but active in U-937 and Ml cells, the latter two being predetermined for macrophags differentiation. Egr-1 anttsense oligomers in the culture media blocked macrophage differentiation in both myeloid leukemia cell lines and normal myeloblasts. HL-99 cells constitutively expressing an Egr-7 transgene (HL-tlOEgr-1) could bs induced for macrophage, but not granuiocyte, differentiation. These observations indkate that expression of Egr-7 is essential for and restricts differentiation of myeloblasts along the macrophage lineage.