Methods are now available to characterize Kupffer cells both in vivo and in vitro. They can be isolated and purified from the liver and their functional activities studied in maintenance culture. Kupffer cells are not merely phagocytic cells or scavengers but they can also produce and secrete a variety of substances that can regulate the functions of other cells. They can also regulate the immune system and be directly cytotoxic to tumor cells and parasites. In the light of these reported functions, the clinical importance of Kupffer cells in a variety of liver diseases deserves to be better explored. Although the origin and cytokinetics of Kupffer cells, and specially their relation to the Mononuclear Phagocyte System (MPS), are still not completely understood, it has now become clear that Kupffer cells are not end-cells incapable of self-proliferation. Under various experimental conditions Kupffer cells have been shown to respond to activation by strong mitotic proliferation. On the other hand, bone marrow-derived cells can migrate to the liver under certain conditions and differentiate into liver macrophages, thus becoming Kupffer cells.