The receptor-mediated degradation of 125I-low density lipoprotein (LDL) was compared in normal white blood cells and leukemic cells. The cells were isolated from the peripheral blood and bone marrow of healthy subjects and patients with newly diagnosed leukemia. The cells from most of the 40 consecutive patients with acute myelogenous leukemia showed markedly higher degradation rates as compared to mononuclear cells and granulocytes from peripheral blood and nucleated cells from the bone marrow of healthy individuals. Leukemic cells from patients with monocytic (FAB-M5) or myelomonocytic leukemia (FAB-M4) exhibited the highest degradation rates. The rate of receptor-mediated degradation of 125I-LDL was also high in leukemic cells from all three patients with chronic myelogenous leukemia in blast crisis, as well as in two of three patients with acute undifferentiated leukemia. In contrast, leukemic cells isolated from two patients with acute lymphoblastic leukemia showed low rates. In most cases, there was little difference in LDL receptor activity between leukemic cells isolated from peripheral blood and those from bone marrow. Hypocholesterolemia was a frequent finding in the leukemic patients. There was an inverse correlation between the plasma cholesterol level and the rate of receptor-mediated degradation of 125I-LDL by the leukemic cells. Studies are now in progress to investigate the possibilities of using LDL as a carrier of cytotoxic drugs in the treatment of leukemia.