The distribution and endocytotic function of Kupffer cells in the rat liver were studied after administration of fibrinogen stabilized colloidal gold suspensions either by injection directly into the circulatory system of anaesthetized rats or by application to the isolated perfused liver. After exposure to gold particles the livers were perfused with fixative and studied using several microscopic techniques. Gold was predominantly endocytosed by a highly active population of Kupffer cells surrounding the portal spaces resulting in distinct dark patterns around the terminal portal veins. In cross-sections of lobules the pattern appeared as incomplete networks composed of dark triangular areas with distinct borderlines towards light areas concentric with the terminal hepatic veins (central veins). The light areas contained few and relatively inactive small Kupffer cells. A wide variation of conditions gave essentially the same uptake pattern compatible with the concept of microcirculatory zones concentric with the terminal hepatic veins (Lamers et al., 1989; Quistorff and Rømert, 1989), but contradicting the traditional view of microcirculatory zones advanced by Rappaport et al. (1954). Since the same pattern developed during conditions of anoxia, it seems that oxygen is not the stimulus for the developmental distribution of Kupffer cells with high endocytotic activity. In vivo and perfusion experiments gave identical patterns, but a higher endocytotic activity of endothelial cells was found in perfused isolated livers.