The characteristics of the recognition system involved in the binding of galactose-exposing particles to freshly isolated rat Kupffer cells were determined. For this purpose we used iodinated lactosylated low-density lipoprotein (125I-Lac-LDL) as a ligand for the galactose receptor on Kupffer cells. The affinity of the binding of 125I-Lac-LDL to Kupffer cells was saturable (23,500 galactose-specific binding sites per cell) and of high affinity (2.4 +/- 0.3 nM). The order of potency of various carbohydrates in inhibiting the association of 125I-Lac-LDL with Kupffer cells was as follows: N-acetylgalactosamine > L-fucose >> N-acetylglucosamine/mannan. Association of 125I-Lac-LDL with Kupffer cells in the absence of Ca2+ was at the same level as in the presence of 50 mM N-acetylgalactosamine. A polyclonal antibody raised against the rat asialoglycoprotein receptor inhibited the binding of 125I-Lac-LDL to Kupffer cells and reacted in a Western blot with two proteins (molecular mass 88 and 77 kDa), which correspond to the molecular mass of the fucose receptor [Lehrman, Haltiwanger and Hill (1986) J. Biol. Chem. 261, 7426-7432]. Furthermore, the ability of fucosylated neoglycoproteins to displace 125I-Lac-LDL from Kupffer cells was equally dependent on the extent of fucosylation as previously reported for the fucose receptor. We conclude that the fucose receptor and not the C-reactive protein, as recently proposed [Kempka, Roos and Kolb-Bachofen (1990) J. Immunol. 144, 1004-1009], functions as the galactose-particle receptor on the Kupffer cell. The binding of galactose-exposing particles to the fucose receptor is a previously unknown property of this receptor.