It has been postulated that the selective accumulation of circulating desialylated cells in the mammalian liver results from the binding of desialylated glycoproteins on surfaces of the cells to asialoglycoprotein receptors in the liver. Since circulating cells in the liver are in contact predominantly with sinusoidal lining cells (Kupffer cells and endothelial cells), this postulate requires the presence of asialoglycoprotein receptors on the luminal surface of the sinusoidal lining cells. Whether the receptor is present on these cells, however, remains controversial. To clarify this issue, we used an indirect immunoelectron microscopic method to determine the distribution of the receptor on the surfaces of hepatic cells accessible to the circulation. F(ab')2 fragments of antireceptor antibodies were perfused in situ via the portal vein prior to tissue fixation. After perfusion fixation, sections were reacted with peroxidase-labeled antibodies to the antireceptor F(ab')2. The plasma membranes of Kupffer cells, endothelial cells, and fat-storing cells were devoid of the asialoglycoprotein receptor. In contrast, the receptor was associated with hepatocytes, where it was present diffusely on the sinusoidal plasma membranes and concentrated within coated pits. We conclude that it is unlikely that circulating desialylated cells bind to the asialoglycoprotein receptor in the liver unless a breach in the continuity of sinusoidal lining cells exists.