1. Diadenosine tetraphosphate (Ap4A) levels were determined in HL-60 cells differentiating into granulocytes or monocytes after treatment for 0-7 days with retinoic acid (RA) or 4-beta-phorbol-12-myristate-13-acetate (PMA) respectively. 2. The levels increased significantly compared to untreated control cells within 2 days and then declined again. 3. In RA treated cells the levels finally decreased far below those of untreated HL-60 cells and became equal to those found in human granulocytes. 4. PMA treatment had no effect on Ap4A levels in human granulocytes. 5. A possible interaction between Ap4A and ADP-ribosyl transferase is discussed.