The ability to isolate homogeneous populations of antiviral T lymphocytes from immune mice has led to insight into a variety of areas in cellular immunology. It has permitted the characterization of the distinct pathways of antigen processing and presentation to CD8⁺, Class I MHC-restricted and CD4⁺, Class II MHC-restricted cytolytic T lymphocytes as well as the identification of antigenic epitopes for T lymphocytes. In addition,in vivoeffector function of CD8⁺and CD4⁺cytolytic T-cell clones in protection from lethal viral pneumonia in a murine model of influenza virus infection has been demonstrated. Since the identification of CD4⁺T-lymphocyte helper subsets based on the lymphokine profiles of clonal populations, much interest has been focused on the role of specific cytokines in ultimately determining the effector functions of those cells. The protocol presented in this paper has been used to isolate Th1 and Th2 clones in a viral infectious disease model that has enabled us to further investigate the role of specific cytokines in controlling viral infection.