Many organisms, including several parasites, fungi, some viruses, and intracellular bacteria, are able to survive and multiply in the phagocytes which harbor them. The ability of mice to resist infection by the intracellular bacterium, L. monocytogenes, has provided a good model for studying resistance to infection by intracellular organisms. However, rigid dissection of non-specific and immunologically specific components of resistance, and the cells which mediate them, has not yet occurred. We have developed two experimental systems which will allow us to identify both cells and mechanisms involved in specific and non-specific resistance to Listeria. First, we have demonstrated that lethally-irradiated mice injected with normal isologous bone marrow cells are even more resistant to infection than are normal untreated mice. Since mature populations of B lymphocytes, T lymphocytes, macrophages, or combinations of these cells cannot reproduce this short-term, non-specific resistance, we can now ask whether mature granulocytes, or the recently described M cells, are responsible for bone marrow transfer of resistance; or whether it is the precursors of hematopoietic cells which produce this effect. The second experimental system we will use takes advantage of the ability of Listeria components and other materials, when injected intraperitoneally along with a challenge inoculum, to decrease resistance to Listeria. This decreased resistance is partly specific and partly non-specific, and provides an easy system for critical analysis of means by which resistance may be decreased. One can gain as much important information regarding resistance to intracellular organisms by analysis of events which decrease resistance as by studying ways to increase resistance. Finally, continued examination of Listeria components which either affect lymphocyte function, on the one hand, or affect macrophage function, on the other hand, will provide additional insight into participation of these cells in resistance.