Murine salmonellosis is used as the experimental model to resolve the current controversy of whether pathogenic salmonellae do survive and multiply within host phagocytes. Electron microscopic studies on the peritoneal exudate cells and on the liver of mice infected with Salmonella typhimurium have now shown that salmonellae are killed within inflammatory polymorphs and macrophages and multiply in the extracellular space and within hepatocytes. Continuation of this project in the next three years will be directed (a) to certify that the bacteria seen in the tissues are in fact salmonellae and that intracytoplasmic debris seen in the phagocytes does contain salmonella antigens, using immunocytochemical techniques (such as immunofluorescent staining, glucose oxidase and colloidal gold labeling) in light and electron microscopy; (b) to develop a tissue embedding method so that serial sections can be made for histopathological and immunocytochemical staining for use both in light and electron microscopy; (c) to determine whether there is any difference in the preferential location of bacterial proliferation in host tissues and, in particular, the role of the macrophages in salmonellosis, by comparing genetically resistant versus susceptible mice infected with salmonellae. The project is considered as a crucial step in the elucidation of pathogenesis of and immunity in murine salmonellosis, particularly in view of the current interest in the genetic variations of host response to infection. Such a definitive study is essential in providing the basis for the development of salmonella vaccines.