Cytolysis of leukemic cells by peripheral blood-derived macrophages was examined by means of an in vitro 111In release assay. Monocytes prepared on culture dishes lyse YK-M2. However, when monocytes were cultured in vitro and transformed into macrophages, they lost most of their lytic activity. The addition of human recombinant interleukin-2 (rIL-2) on day 5 in culture enhanced the lytic activity significantly. Similarly, treatment of macrophages with human recombinant interferon gamma (rIFN-gamma) promoted the lysis of YK-M2 and K-562, although the extent of lysis was smaller than that by rIL-2. Macrophages activated with rIL-2 and rIFN-gamma also lysed human leukemic cells. Activated macrophages lysed leukemic cells of acute myelocytic leukemia more than acute lymphocytic leukemia cells. Macrophages derived from the peripheral blood of patients with leukemia were examined for their lytic activity against YK-M2. The patient's macrophages lysed more YK-M2 than did control macrophages when they were activated with rIL-2 and rIFN-gamma. The macrophages of two patients also demonstrated autologous leukemic cell lysis.