The purpose of this study was to determine (1) the number and activity of natural killer (NK) cells in children with acute leukemia at different stages of their disease; and (2) the effect of interleukin-2 (IL-2) in enhancing NK activity of these patients' cells. The mean percentage of Leu 11+ NK cells in patients at diagnosis (5% of peripheral blood (PB) mononuclear cells) was significantly lower than for patients on maintenance (23%), post-treatment (21%) and for normal children (20%). The mean PB NK cell cytotoxicity for patients at diagnosis (16% lysis versus K562) and during maintenance (20%) was significantly lower than for post-treatment (41%) and normal controls (40%). After NK cells were incubated for 5 days with IL-2, NK cells from 82% (36/44) of patients showed enhanced cytotoxicity toward K562 and several acute leukemia cell lines as well as toward autologous leukemic cells. Cytotoxicity toward autologous cells was very low (0% to 5%, 16 hour assay) before IL-2 stimulation, and significantly increased (23% to 69%) after stimulation, suggesting that IL-2 may be a useful agent for enhancing the antileukemic immune response.