This study investigates the essential role of interferon γ (IFN-γ) in resistance to *Mycobacterium tuberculosis* infection. The authors used genetically modified mice (gko) that lack the ability to produce IFN-γ due to a targeted disruption of the IFN-γ gene. These gko mice, when infected with *M. tuberculosis*, develop granulomas but fail to produce reactive nitrogen intermediates (RNI), leading to a rapid and fatal course of tuberculosis. In contrast, control mice exhibit heightened tissue necrosis and succumb to the infection more slowly. Treatment with exogenous recombinant IFN-γ can delay but not prevent mortality in gko mice. The study also found that gko mice produce significantly less RNI and have reduced levels of nitric oxide synthase (NOS) mRNA, which are crucial for macrophage activation and the production of RNI. These findings suggest that IFN-γ is essential for the immune response to *M. tuberculosis* and that its deficiency leads to a more severe form of the infection. The implications of these results are discussed in the context of tuberculosis in immunocompromised individuals, particularly those with HIV infection.This study investigates the essential role of interferon γ (IFN-γ) in resistance to *Mycobacterium tuberculosis* infection. The authors used genetically modified mice (gko) that lack the ability to produce IFN-γ due to a targeted disruption of the IFN-γ gene. These gko mice, when infected with *M. tuberculosis*, develop granulomas but fail to produce reactive nitrogen intermediates (RNI), leading to a rapid and fatal course of tuberculosis. In contrast, control mice exhibit heightened tissue necrosis and succumb to the infection more slowly. Treatment with exogenous recombinant IFN-γ can delay but not prevent mortality in gko mice. The study also found that gko mice produce significantly less RNI and have reduced levels of nitric oxide synthase (NOS) mRNA, which are crucial for macrophage activation and the production of RNI. These findings suggest that IFN-γ is essential for the immune response to *M. tuberculosis* and that its deficiency leads to a more severe form of the infection. The implications of these results are discussed in the context of tuberculosis in immunocompromised individuals, particularly those with HIV infection.