Murine T cell clones with specificity for the intracellular bacterium Listeria monocytogenes were used in an attempt to analyze the relative roles of helper and cytolytic T lymphocytes in antibacterial immunity. After stimulation by antigen and accessory cells, L. monocytogenes-specific, L3T4+, class II-restricted T cells produced multiple lymphokines, including interleukin 2 and interferon-gamma (IFN-gamma). Cloned T cells could help B lymphocytes differentiate into antibody-secreting cells and could activate antimicrobial macrophage functions in vitro. Furthermore, cloned T cells could confer local protection and delayed-type hypersensitivity. Factors produced by cloned T cells in vitro as well as recombinant IFN-gamma induced antibacterial resistance in vivo. After stimulation by recombinant interleukin 2 and infected stimulator cells, L. monocytogenes-specific, Lyt2+, class I-restricted T cells produced IFN-gamma. Cloned T cells were capable of lysing L. monocytogenes-infected macrophages. It was concluded that both helper and cytolytic T-cell functions are relevant to antibacterial immunity. The possible protective and pathologic effects of helper and cytolytic T lymphocytes, respectively, during infections with intracellular bacteria are discussed.