We could recently show that rat liver macrophages (Kupffer cells) express a membrane-bound form of C-reactive protein on their surface. Because it is removed by washing the cells in buffers containing Ca(++)-chelators, membrane-bound C-reactive protein is a peripheral protein rather than an integral part of the Kupffer cell membrane. This Kupffer cell membrane-bound C-reactive protein is identical to the galactose-specific particle receptor previously characterized. We now present evidence that Kupffer cells do not acquire soluble serum C-reactive protein but synthesize their own membrane-bound C-reactive protein. By RNA-RNA in situ hybridization, it was found that hepatocytes are not the only sort of liver cells synthesizing C-reactive protein, but C-reactive protein-specific mRNA is present also in Kupffer cells. During acute-phase response C-reactive protein mRNA is found in increased amounts within liver macrophages too. Furthermore, by labeling experiments with antisera against native, pentameric soluble serum C-reactive protein and monoclonal antibodies against a neoepitope present on C-reactive protein subunits only, we could establish that the membrane-bound C-reactive protein expressed on the liver macrophage is not the pentameric molecule of soluble serum C-reactive protein, but rather consists of C-reactive protein subunits. Finally, we present evidence that liver macrophages contain a binding protein in their plasma membrane, with an apparent molecular weight of 59 to 61kD, specific for C-reactive protein and similar to the one previously isolated from macrophage cell lines.