Several human acute myeloid leukemia cell lines were recently established. These lines provide model systems to study the control of differentiation in human myelogenous leukemia and, in a broader framework, the controls of normal myeloid development. The K562 line is composed of undifferentiated blast cells that are rich in glycophorin and may be induced to produce fetal and embryonic hemoglobin in the presence of hemin. The KG-1 cell line is composed predominantly of myeloblasts and promyelocytes. A unique characteristic of the KG-1 cells is their almost complete dependence on colony-stimulating factor for proliferation in soft-gel culture. The HL-60 is a promyelocytic leukemia cell line. In the presence of DMSO, the cells mature into granulocytes. Both the KG-1 and HL-60 cells differentiate into nondividing mononuclear phagocytes when exposed to phorbol esters. Investigations with these cell lines, and selected variants should provide important insights into the cell biology and perhaps therapy of human leukemia.