The present study investigated the susceptibility of human leukemia cells to allogeneic lymphocytes with lymphokine-activated killer (LAK) activity from normal donors and autologous LAK activity from patients in complete remission. LAK activity was generated from peripheral-blood mononuclear cells cultured for 6 days with 1,000 U/ml recombinant interleukin-2 (IL-2). Cytotoxicity was evaluated using a standard 4-hour chromium release assay. Susceptibility of leukemic cells to LAK was defined on the basis of the mean Cr release in 52 samples of normal bone marrow cells. Using allogeneic LAK, we examined leukemic cells from bone marrow or peripheral blood of 252 patients [102 with acute myeloid leukemia (AML), 99 with acute lymphoblastic leukemia (ALL), 13 with chronic myelogenous leukemia in blast crisis (CML-BC) and 38 with chronic leukemias of various types]. A significant lysis could be detected in 62% of all leukemias tested (in 68% of AML, 60% ALL, 92% CML-BC, 39% chronic leukemias). The mean chromium release (effector-to-target cell ratio 50:1) was 28.8 +/- 13.5% for LAK-sensitive leukemias versus 5.2 +/- 3.2% for resistant leukemias. We observed a distinct susceptibility of various leukemia subtypes. LAK cytotoxicity against autologous leukemia cells was examined in 40 leukemia patients in complete remission (24 AML, 16 ALL). 63% of the patients developed a significant cytotoxicity against their autologous leukemia cells. Regarding mean Cr releases, the efficiency of allogeneic LAK activity of normal donors did not differ significantly from that of autologous LAK activity of patients in complete remission against the same leukemic target cells. Analysis of our data revealed that examinations with allogeneic LAK activity make it possible to predict whether patients will develop significant in vitro killing of their autologous leukemia cells during complete remission. These results may be of particular importance in determining which patients could benefit from immunologic therapy modalities and in scheduling immunotherapy. Further clinical studies are necessary to ascertain the clinical significance of therapeutic approaches with IL-2 or adoptive cellular immunotherapy combined with IL-2 for treatment of human leukemia.