The liver appears to be an organ favoring the induction of immune tolerance rather than immunity. Among the hepatic cell populations possibly involved in regulation of immune responses, liver sinusoidal endothelial cells (LSEC) are well suited to fulfill this role. LSEC are resident cells lining the hepatic sinusoidal wall and therefore are in intimate contact with leukocytes passing through the liver. They are equipped with numerous scavenger receptors rendering antigen-uptake in these cells extremely efficient. Antigen processing and MHC-restricted presentation of exogenous antigens for CD4 as well as CD8 T cells occurs equally with high efficiency. Importantly, CD4 and CD8 T cells that engaged in cognate interaction with LSEC have a tolerant phenotype. Thus LSEC contribute an important immune function to the liver: control of the immune response against circulating soluble antigens.