The peritoneal IFN-␥ response promotes resistance to LCMV infection. After i.p. infection, LCMV was difficult to detect in lavage fluids at 20 and 24 h, but titers rapidly increased by 30 h and subsequently decreased (Fig. 6A) . To determine the physiologic relevance of the peritoneal IFN-␥ response, viral burdens were measured in samples collected from WT mice and mice rendered unresponsive to IFN-␥ as a result of genetic mutation of the IFN-␥ receptor (IFN-␥R Ϫ/Ϫ ) (25) . The IFN-␥R-deficient mice had significant increases in LCMV titers of approximately 1 log at 30 h after infection (Fig. 6A) . Experiments evaluating the require- ment for NK cells demonstrated that in comparison to control antibody treatments, antibodies to NK1.1 depleted the following: (i) the NK cells from the PECs isolated from uninfected and infected mice (Fig. 6B) , (ii) the major population expressing intracellular IFN-␥ after infection (Fig. 6B) , and (iii) the levels of detectable IFN-␥ in lavage fluids collected at 30 h following challenge (Fig. 6C) . The effects were accompanied by proportional increases in viral titers (Fig. 6C ). Taken together, these studies demonstrate that the IFN-␥ responses have an impact on controlling the viral burden in the peritoneal cavity during LCMV infection and that NK cells are required for the optimal IFN-␥ response, and its effects.