The surface negative charge distribution of fresh leukemic cells from patients with acute leukemia was examined with cationized ferritin (CF), an electron dense label of anionic sites and compared with leukemic cells from phase-cycle fractionated populations of a human leukemic cell line K-562. Normal-untreated and phytohemagglutinin (PHA)-transformed lymphocytes were also tested. A CF-induced redistribution of anionic sites into clusters and patches within a wide range of variations in density was observed electron microscopically both in fresh acute leukemic cells and in unseparated cells of the K-562 line. Cells of the G0/G1 fraction from a phase-cycle separated K-562 population exhibit a higher density of CF label per unit length of membrane as compared with the G2 + M cell fraction. PHA-benign transformed normal lymphocytes exhibit an even and continuous CF labeling, similar to that of normal-untreated lymphocytes. An attempt was made to correlate the CF-induced charge redistribution with the rate of agglutination with the cationic Poly-L-lysine. Our observations indicate that the CF ligand does induce an anionic site redistribution, varying in density, both in fresh leukemic cells and in cells from a K-562 line, and does not in normal untreated and PHA-benign transformed lymphocytes. The particular pattern of anionic site redistribution observed in leukemic cells of this study is apparently phase-cycle dependent.