Immune interferon, available at high specific activity through recombinant DNA technology, is known to activate macrophages to intra‐ and extracellular cytotoxicity. We now report that murine recombinant IFN‐γ activates macrophages to cytotoxicity also when applied in vivo. Furthermore, recombinant IFN‐γ can protect mice in vivo against the intracellular bacterial pathogen Listeria monocytogenes in a local as well as in a systemic infection model. The role of T lymphocyte‐produced lymphokines in acquired resistance to facultative intracellular pathogens and their possible involvement in novel immunotherapy are discussed.