As part of our ongoing studies on the interaction of interleukin 2 (IL-2) with natural killer (NK) cells, we recently demonstrated that clonogenic cells from human tumors are targets for autologous peripheral blood mononuclear cells (PBMC), especially IL-2-primed PBMC. Fresh human tumor cell suspensions cocultivated with autologous IL-2-primed PBMC gave rise to fewer colonies in soft agar than unexposed tumor cells or cells cocultivated with resting PBMC. In preparation for clinical trials with recombinant IL-2, we have compared recombinant IL-2, purified by sequential gel filtration and preparative SDS-PAGE, with purified IL-1 for the ability to induce fever, acute phase protein, and prostaglandin synthesis in rabbits and have found that, unlike IL-1 and alpha interferon, IL-2 is not intrinsically pyrogenic. We have developed a sensitive ELISA for the detection of anti-IL-2 antibodies in humans receiving IL-2 and have developed a rabbit heteroantiserum that neutralizes the biological activity of the lymphokine. We have preliminary data demonstrating the presence of such antibodies in some patients with SLE and will ascertain whether such antibodies develop in patients given recombinant IL-2 in a Phase I clinical trial recently initiated at our institution. We have also begun a series of experiments to determine the alterations in large granular lymphocyte (LGL) membrane proteins induced by exposure to IL-2. These studies consist of the generation of a series of monoclonal antibodies specific for IL-2-primed LGL and the comparative analysis of membrane proteins of resting and IL-2-stimulated LGL by two-dimensional PAGE. These experiments will clarify the role of IL-2 in the activation of human LGL. (HF)