A human common acute lymphoblastic leukemia (ALL) cell line, REH, was treated in vitro with gamma-interferon (gamma-IFN) or 12-O-tetradecanoylphorbol 13-acetate (TPA). Untreated (control) and treated cells were analyzed for changes in growth patterns, morphology, cytochemistry, surface phenotype, and terminal transferase (TdT) activity. TPA but not gamma-IFN induced further maturation of REH cells along the B-cell lineage. There was a dramatic decrease in CALLA expression, loss of TdT activity, induction of Leu M5, and increase in Leu 14 expression. TPA also induced monocytoid morphological features on REH cells. Enzymatically, the induced cells strongly expressed acid phosphatase (tartrate sensitive), alpha-naphthol acetate esterase (NAE), and periodic acid Schiff (PAS). We conclude that TPA induced monocytoid B-lymphocyte features on REH cells within the B-cell lineage, which should not be confused with monocytes/macrophage. The phenotype of cells in this stage is Leu 14+, Leu M5+, BL1+, Leu 12+, AcP+, PAS+, NAE+, CALLA-, TdT-, MO1-, and MO2-.