Listeria monocytogenes normally infects the host by translocating from the intestinal lumen. Experiments were carried out to determine if, when, and where tumor necrosis factor (TNF) and gamma interferon (IFN-) function in antibacterial resistance during enteric listeriosis. Groups of normal mice and severe combined immunodeficient (SCID) mice were injected with neutralizing monoclonal antibodies (MAb) specific for each cytokine and then inoculated intragastrically with L. monocytogenes. The course of infection was monitored by enumerating listeriae in gut-associated lymphoid tissues, livers, and spleens. By the third day of infection, bacterial numbers in infected tissues and organs were greatly exacerbated in all mice treated with anti-TNF MAb, whereas bacterial numbers in the organs of mice treated with anti-IFN- MAb did not differ from those present in the respective organs of control mice. However, by the fifth day of infection, bacterial numbers in the organs of anti-IFN- MAb-treated normal mice and SCID mice were much greater than in the corresponding organs of control mice. Experiments with Listeria-immune mice revealed that TNF and IFN- are involved in the expression of anti-Listeria memory immunity; however, it was also found that the anti-IFN- MAb was relatively ineffective in inhibiting the expression of anti-Listeria immunity, whereas a polyclonal anti-IFN- was quite effective.