Natural killer (NK) cells are an important part of the innate immune response. They have the ability to recognize and kill many types of tumor cells and promote immunity against intracellular pathogens. In this study, we analyzed the in situ localization of NK cells within wildtype and immunodeficient mice using a novel in situ analysis method. We have identified NK cells in tissues of B6 and B6.Rag1(-/-) mice and demonstrated an increase in the percentage of NK cells and the total number of NK cells in the lung and liver of immunodeficient mice. This increase was not due to an increase in NK cell activation. This study describes a means to identify NK cells within complex tissue environments, and the increase in NK cells in non-lymphoid tissues may explain much of the increased NK cell activity observed in T-cell-deficient mice.