Newly developed methods for lymphoid cell analysis, growth in culture, and cloning offer the promise of more effective strategies for the control of malignancy. Experimental models are required to test and refine these potential treatments and determine their applicability to naturally occurring cancers. In a unique model system developed in our laboratory, leukemia in mice undergoes predictable immunologically mediated spontaneous regression. Normal T-cell and macrophage function are essential for regression to occur, and in leukemic animals that are going to regress, specifically reactive T cells are found in the spleen. Leukemic regression is efficiently induced in progressor leukemic mice with the transfer of in vitro-cultured T cells that are specifically reactive against viral antigens. The cultured T cells demonstrated high levels of virus-specific, in vitro cytotoxicity. Therapy is effective even in fully leukemic mice and requires no prior or adjunctive irradiation or cytotoxic drug treatment. T cells of the Lyt 1+ subclass cure leukemic animals, while Lyt 2+ cells cause only temporary remission of the disease. Our goals for the coming year are to extend our present studies to include in vitro cloning and expanding the T cells active in vivo transfer of leukemia regression, further definition of the T-cell population responsible for this activity, determination of the viral antigenic specificity of the reactive T cells, and investigation of the possible use of T cells in preventing leukemia recurrence. (LB)