Lymphocyte‐mediated inflammation is a hallmark of autoimmune diseases, such as multiple sclerosis, Crohn's disease, rheumatoid arthritis and sarcoidosis. However, this type of inflammation probably developed under evolutionary pressure from pathogenic microorganisms, such as mycobacteria and other intracellular infective agents. One such pathogen, the gram‐positive bacterium Listeria monocytogenes (L. monocytogenes), induces a cascade of tissue alterations that ultimately results in the eradication of the bacteria associated with a granulomatous response. Consequently, murine listeriosis has been established as a model to analyze not only T‐cell‐dependent antibacterial protection but also T‐cell‐mediated mononuclear inflammation in parenchymal organs. Extensive studies of the molecular basis of the latter phenomenon led to the conclusion that the most decisive step from non‐specific microabscess formation to granulomatous inflammation is the activation of non‐specifically invading CD4⁺ T cells, which results in high local concentrations of TNF‐α and IFN‐γ in the presence of IL‐2. This in turn induces CD11b‐independent mechanisms of intraparenchymal monocyte accumulation. Because any attempt to neutralize the effects of TNF‐α and IFN‐γ to modulate T‐cell‐mediated inflammation will also dramatically decrease host resistance, other anti‐inflammatory strategies based on the modulation of TNF‐α and IFN‐γ‐induced mechanisms of monocyte accumulation must be developed. Recalling the classical work by Dienes & Schoenheit on the induction d bacterial allergies (1), the cytokine phenotype of granuloma formation also has implications as regards the most potent adjuvant environment for the development of a T‐cell response. The murine listeriosis model is the basis for all conclusions in this article on the role of cytokines in the induction and expression of T‐cell‐mediated inflammation and. as we will show, promises to yield still more insights into the rational design of vaccines.