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The reticuloendothelial system was the name originally proposed by Aschoff for a system of cells of great morphological diversity linked together by the property of phagocytosis1. This cell system comprises endothelial cells, fibrocytes, reticular cells of spleen and lymph nodes, reticuloendothelial cells of lymph and blood sinuses including Kupffer cells, histiocytes, splenocytes and monocytes. Several attempts have been made through the years to find a better descriptive term than the reticuloendothelial system. The most recent proposal, and generally an acceptable one, has been the introduction of the term mononuclear phagocyte system, ‘comprising a group of cells that are related by similarities of morphology, function and origin’2. This mononuclear phagocyte system (MPS) comprises precursor cells (in the bone marrow), promonocytes (in the bone marrow), monocytes (in the bone marrow and in the blood) and macrophages in connective tissue (histiocytes), liver (Kupffer cells), lung (alveolar macrophages), spleen (free and fixed macrophages), lymph nodes (free and fixed macrophages), bone marrow (macrophages), serous cavities (pleural and peritoneal macrophages), bone tissue (osteoclasts), and nervous system (microglial cells). The part of the mononuclear phagocytic system to be described here is the system of macrophages in the liver, the Kupffer cells. Most studies concerned with the MPS have not made a distinction between Kupffer cells and other macrophages but described the system as a whole. However, the fact that the Kupffer cells comprise by far the greatest part of the MPS, together with their strategic localization in relation to the blood flow from the gastrointestinal tract, justifies discussing them as a special entity. In recent years the idea has repeatedly been put forward that the function of these cells is different from other phagocytic cells, especially with regard to immune phenomena. In this chapter we wish to describe the functions of the Kupffer cells with special emphasis on their role in immune processes.