The liver is known for its ability to induce antigen (Ag)-specific immune tolerance. Among the different cell populations involved in the induction of hepatic tolerance, the liver sinusoidal endothelial cells (LSECs) are particularly important because they are highly efficient at presenting soluble Ags to CD4(+) and CD8(+) T cells. The crosspresentation of soluble Ags to CD8(+) T cells was believed previously to be restricted to professional Ag-presenting cells (APCs) such as dendritic cells (DCs). However, in contrast to DCs, crosspresentation by LSECs can induce Ag-specific immune tolerance. It is proposed that these organ-resident APCs act as sessile hepatic APCs that control the immune responses to soluble blood-borne Ags, in concert with APCs in lymphatic tissue.