To help understand host-tumor relationships in adult acute lymphoblastic leukemia (ALL) and to better define potential indications for interleukin-2 (IL-2) treatment in this disease, the relationship between the susceptibility of leukemia cells of 22 patients with ALL to lysis by allogeneic lymphokine-activated killer (LAK) cells and characteristics of the leukemia was studied. Lymphocytes were activated in the presence of 1000 U/ml recombinant IL-2 for 5 days. The lysis of ALL cells was studied by the release of 51Cr. The average lysis of ALL cells by control, unactivated lymphocytes was 1.2 +/- 2.4% and by LAK cells 8.9 +/- 8.6%. The susceptibility of leukemic cells to lysis did not correlate with the expression of lymphoid or myeloid differentiation markers or expression of the adhesion molecules CD54 (ICAM-1) and CD58 (LFA-3). Leukemic cells of the FAB I2 subtype were significantly more resistant to lysis than those of the other subtypes (average lysis 1.4 +/- 3.0% versus 12.3 +/- 8.2%, p = 0.003). The susceptibility to lysis did not correlate with the other initial characteristics of the leukemia. The 11 patients in whom 8% or more of leukemic cells were lysed by allogeneic LAK cells survived significantly longer than the 11 patients whose blast cells were less susceptible to lysis (p = 0.04). It is concluded that IL-2 treatment might be of benefit in adult ALL, particularly in non-L2 FAB subtypes and during complete remission to possibly delay relapse and prolong survival.