CD34 is one of the best characterized human hematopoietic stem cell antigens defined to date. It is expressed on 1% to 4% of normal bone marrow cells, including colony forming units of all lineages and their precursors. CD34 expression is lost during hematopoietic development and is not found on mature peripheral blood cells. The control of CD34 expression was studied in the myeloblast cell line KG-1 as a model for the regulation of stem cell genes. CD34 mRNA was expressed at high levels in uninduced KG-1 cells. Upon induction of the cells towards macrophages with tetradecanoylphorbol-13-acetate (TPA) and ionomycin, steady state levels of CD34 mRNA decreased rapidly. Nuclear run-on assays did not show a significant change in the rate of CD34 transcription upon induction. The half-life of CD34 mRNA was 4.5 hours in uninduced KG-1 cells and 2.25 hours in induced cells, demonstrating the involvement of post-transcriptional mechanisms in CD34 downregulation. Cycloheximide had no effect on the downregulation of CD34, suggesting that labile proteins are not required for this process. This model should allow the study of some of the regulatory mechanisms controlling early events in hematopoiesis.