Recent progress in biotechnology has uncovered the presence of trace substances which participate in the immunological response between cancer and host, they are cytokines, monoclonal antibodies, and immunomodulating agent which are called as biological response modifiers (BRM). The genetic engineering enables mass production of these substances, and their clinical application in treating hematological malignancies is expected. The role of biologically active substances as important pharmacological reagents was initially explored in human with purified interferon. The most recent example of such rapid progress has been with IL-2 and TNF. Clinical trials with recombinant IL-2 and TNF have begun in 1984. Although IL-2 is effective for the activation of T lymphocyte, intravenous injection of IL-2 was not so effective for treatment of hematological malignancies. On the other hand, IL-2 activated Killer cells were potent effectors of adoptive immunotherapy. Tumor necrosis factor, a cytotoxin derived from macrophages showed marked decreases in percentage of leukemic cells of peripheral blood in treating leukemic patients.