Exposure of Leishmania major-infected CBA/T6 mouse macrophages to lymph node cells (LNC) from infected animals led to antigen-specific killing of the micro-organisms. The effect depended on the number of added LNC, the duration of incubation with macrophages, and the presence of LPS in the incubation fluids. Incubation with immune LNC also resulted in lysis of part of the infected cells, however without release of live amastigotes, as parasites were destroyed intracellularly before macrophages were damaged. Supernates from antigen-stimulated LNC cultures activated macrophages for intracellular killing without damage to the host cells, suggesting that macrophage lysis was not a consequence of the activation process. Treatment of effector lymphocytes with anti-L3T4 antibodies abrogated both intracellular killing and macrophage lysis. Parasitized macrophages were also destroyed by alloimmune cytolytic T-lymphocytes; in this case, however, live amastigotes were released, showing that immune lysis of the infected cells would not entail parasite destruction per se. These studies support the hypothesis that recovery from L. major infection relates to the ability of lymphoid cells to generate MAF/IFN in response to parasite antigen and are compatible with the idea that lysis of parasitized macrophages may contribute to immune recovery from the infection.