Leukemic cells from patients with acute myeloid leukemia underwent morphological, functional, and histochemical changes within 24–48 hr after treatment with 1.6 x 10–18 M 12–0-tetradecanoylphorbol-13-acetate (TPA). The changes included adhesion to the plastic substrate, a 4–6- fold increase in the number of phagocytic cells, and an increase in the number of alpha-naphthyl-acetate esterase (alpha-NAE) positive cells. In contrast, TPA treatment of cells from patients with acute lymphoblastic leukemia caused some aggregation of cells in suspension, but no changes in adhesion, phagocytosis, or alpha-NAE. Of the four cases of undifferentiated or unclassified leukemias studied, two failed to respond to TPA, one responded with a myeloid (adhesion) pattern, and one with a lymphoid (aggregation) pattern. These data suggest that leukemic myeloblasts retain the ability to express a variety of differentiated functions, and in some cases, it may be possible to use TPA as a tool to test the differentiative potential of undifferentiated human leukemias.