The observation of more frequent leukemias in immune deficiencies of the non-HLA-restricted cytotoxic cell system and the participation of this system in the anti-leukemic effect of allogeneic bone marrow transplantation in acute leukemia indicate that these cells might play a role in the immune surveillance against leukemia. In order to find more direct evidence of this role we studied the susceptibility of leukemic cells to lysis by non-HLA-restricted cytotoxic cells, the functional value of these cells in leukemic patients in complete remission (CR), and expression by leukemic cells of adhesion molecules CD54 and CD58, which play a role in the adherence between cytotoxic cells and their targets. Our results are concordant to confirm a potential role of non-HLA-restricted cytotoxic cells in the immune surveillance of acute leukemia based on increased relapse rate in acute myeloid leukemia patients with no inducible lymphokine-activated killer (LAK) cell activity during CR, short survival of acute lymphoblastic leukemia patients whose blast cells are resistant to lysis by LAK cells, and poor overall prognosis of leukemias which do not express CD58.