The role of the immune response in the chemotherapeutic cure of an intact host with neoplasia is not well defined. We have previously shown that the addition of cyclosporin A to VP-16 therapy of BDF/1 mice with L1210 leukemia produces immunity to leukemia in long-surviving host animals. We now characterize this immunity as being tumor specific and related to the participation of CD8 T-lymphocytes. Splenocytes derived from L1210 leukemia immune mice are cytotoxic to L1210 cells after in vitro restimulation, compared to splenocytes harvested from nonimmune control mice. This cytotoxicity is lost by CD8 T-lymphocyte depletion and persists in Ia antigen blocking experiments. Cytotoxicity is selective for L1210 leukemia compared to P388 leukemia, an alternate Ia antigen expressing methylcholanthrine-induced acute lymphoid leukemia, and L1210 leukemia-immune mice remain susceptible to P388 leukemia in vivo demonstrating specificity of the immune response generated by cyclosporin A/VP-16 therapy.