This study was undertaken to identify the role of scavenger receptors in the catabolism of lipopolysaccharide (LPS) and lipoteichoic acid (LTA). LPS is mainly cleared from the blood by the liver. The Kupffer cells are primarily responsible for this clearance. Although several binding sites have been described for LPS and LTA, only CD14 is involved in LPS signalling. Scavenger receptor type A (SR-A) is expressed in the liver on endothelial cells and Kupffer cells, and macrosialin (class D scavenger receptor) is expressed on Kupffer cells. Fucoidin and poly-I are both good inhibitors of scavenger receptors. Fucoidin significantly reduced the serum clearance of [125I]-LPS and decreased liver uptake of [125I]-LPS by approximately 40%. Poly-I inhibited the binding of [125I]-LPS to isolated Kupffer and endothelial cells by 75%, while poly-A, a polyanionic substrate that does not block scavenger receptors, had no effect. LPS significantly inhibited the binding of acetylated LDL and oxidized LDL (two well-described scavenger receptor ligands) to isolated Kupffer and liver endothelial cells. OxLDL and acLDL did not affect the binding of LPS to these cells. We conclude that on both endothelial cells and Kupffer cells, LPS mainly binds to scavenger receptors, but SR-A and macrosialin contribute to a limited extent to the binding of LPS. Injection of LTA into C57Bl6 mice resulted in a maximal liver uptake of 20% of the injected dose. In the liver, 50% was bound by the Kupffer cells, 20% by parenchymal cells and 30% by liver endothelial cells. The contribution of SR-A to the plasma clearance of LTA was limited. A main component in the catabolism of LTA is the interaction of LTA with plasma lipoproteins, which limit the uptake of LTA by tissues and extend the plasma half-life of LTA.