The murine macrophage-like cell line J774.A1 ingests and allows intracellular growth of Francisella tularensis. We demonstrate that, after 24 h of infection, a pronounced cytopathogenicity resulted and the J774 cells were undergoing apoptosis. Despite this host cell apoptosis, no decrease in bacterial numbers was observed. When internalization of bacteria was prevented or intracellularly located F. tularensis bacteria were eradicated within 12 h, the progression of host cell cytopathogenicity and apoptosis was prevented.