Hepatic sinusoids are highly specialized capillary vessels characterized by the presence of resident macrophages adhering to the endothelial lining. Although it is likely that sinusoidal endothelial cells have specific adaptations, little is known about the roles that they actually play in vivo. We therefore designed an in situ immunophenotyping study of sinusoidal endothelial cells in normal human liver to compare this population with those of the other vascular compartments of the liver and to determine whether it expresses molecules involved in the following physiological processes: scavenging and nonspecific immune functions, antigen presentation and endothelial-leukocyte adhesion. Our study showed that sinusoidal endothelial cells displayed a highly distinctive immunophenotype characterized by the expression of several molecules not found in the other vascular compartments of the liver. A first group of molecules restricted to sinusoidal endothelial cells were: the receptors II and III for the Fc fragment of IgG; the CD14 molecule, serving as a receptor for the lipopolysaccharide-binding protein; and aminopeptidase N. The presence of those molecules suggests that sinusoidal endothelial cells contribute to the scavenger and nonspecific immune functions of hepatic sinusoids. No direct evidence for an antigen-presenting function of this cell population was obtained. Another group of proteins restricted to sinusoidal endothelial cells comprised the leukocyte adhesion molecules CD4 and intercellular adhesion molecule-1, which may be involved in the adhesion of Kupffer cells to the sinusoidal wall. Therefore our immunophenotyping study makes it possible to provide an in situ demonstration of the phenotypical and functional diversity of endothelial cells in normal human liver.(ABSTRACT TRUNCATED AT 250 WORDS)