K562/VCR cells, which are resistant to the cytotoxicity of vincristine, were isolated from human erythroleukemia K562 cells. Various compounds that induce erythroid differentiation of K562 cells were tested on K562/VCR cells. Differentiation of K562/VCR cells was not induced by actinomycin D or adriamycin alone, but the resistance of these cells to the inducers was overcome by verapamil. In contrast, mitomycin C, butyric acid and hemin induced differentiation of K562/VCR cells as effectively as that of K562 cells. These results suggest that therapy by induction of differentiation of leukemic cells is effective for leukemic cells that have acquired resistance to therapeutic drugs.