Recent advances in immunology have led to important insights into leukocyte differentiation and the cellular origin of leukemia. It is now possible to precisely define stages of human lymphocyte and granulocyte differentiation utilizing highly specific monoclonal antibodies that define cell surface antigens in conjunction with more traditional markers such as surface and cytoplasmic immunoglobulin on B lymphocytes, sheep erythrocyte (E) receptors on T lymphocytes, and cytochemical staining of myeloid cells. Five major subtypes of acute lymphoblastic leukemia (ALL) are now recognized, including unclassified or null ALL, common ALL (cALL), pre-B-ALL, B-ALL, and T-ALL. Within the T-ALL subgroup, there is considerable heterogeneity based on the presence or absence of the E-receptor and various T-cell surface membrane antigens defined by monoclonal antibodies. Cells from patients with chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and Sέzary syndrome also can be classified by their reactivity with monoclonal antibodies. Acute myelogenous leukemia (AMD cells are generally classified by morphological and cytochemical features. Recently, monoclonal antibodies reactive with granulocytic and monocytic subtypes of AML have been developed. In addition to their utility in leukemia classification, monoclonal antibodies that identify leukemia associated antigens have also been used therapeutically. Monoclonal antibodies have been infused intravenously into patients with leukemia and lymphoma. They have also been used in vitro with complement to lyse residual leukemia cells from remission bone marrows removed from leukemia patients. These treated bone marrows were later reinfused into the same patients to “rescue” them following high-dose chemotherapy and radiation therapy.