Myeloid leukemic cells can be induced to differentiate by various compounds, suggesting the possibility of controlling leukemia through induced differentiation. For this to be feasible, the growth of leukemic progenitor cells should be inhibited by these compounds, with the inhibition preferentially affecting leukemic over normal hemopoietic progenitor cells. 12-O-Tetradecanoylphorbol-13-acetate (TPA) was chosen as a differentiation inducer and was studied for its effect on the growth of leukemic colony-forming cells (L-CFU) in ten patients with acute nonlymphocytic leukemia in comparison with normal myeloid colony-forming cells (CFU-C). Growth inhibition of both L-CFU and CFU-C was observed with TPA concentrations as low as 10(-10) M. With increasing concentrations of TPA, survival of L-CFU tended to decline more precipitously than that of CFU-C. In eight of ten patients, inhibition of L-CFU was significantly greater (P less than 0.01) than CFU-C with TPA concentrations of 10(-9) M or higher. This study indicates that a compound capable of inducing differentiation of leukemic cells can inhibit growth of leukemic progenitor cells and that this growth inhibition applies preferentially to leukemic cells as compared with normal hemopoietic cells.