Peripheral blood lymphucytes were obtained from 14 patients with advanced cyncer receiving combination therapy with interleukin-2 (IL-2) and a-interferon (a-IFN) as a part of a phase I study and killer cell activities were assayed against k-562 and Daudi cell lines before, during, and after the therapy. There was significant natural killer (NK) activity before the treatment (74+-77 Lytic Unit) and it increased during the treatment (day 5, 262+195 L.U., p<0.01); day 15, 431+-328 L.U., p<0.01; and day 26, 743+-506 L.U., p<0.01). Lymphokine activated killer (LAK) activity before the treatment was low (13+9 L.U.) but also increased significantly during and after the treatment (day 5,71+59 L. U., p<0.01; day 15. 63+-77 L.U.; and day 26, 290+419 L.U.). In l0 patients same assay was repeated during the second course of therapy and showed similar increase in killer cell activities without evidence of cumulative increment. Out study showed that immunotherapy with combination of IL-2 and rz-IFN induces significant levels of NK and LAK cell activities in patients with advanced cancer. This biological phenomena can be utilized as a paramenter with which the IL-2 therapy can be tailored to augment clinical efficacy and tolerability.