A binding protein from liver which binds reversibly to yeast mannan depending on the presence or absence of calcium has been purified to near homogeneity by affinity chromatography. The binding of the isolated protein to 125I-mannan is proportional to protein concentration and is apparently an unsaturable process. The Scatchard plot of the binding is a curvilinear, indicating the presence of a high affinity binding site with a dissociation constant of 1.62 X 10(-8) M. Evidence is presented to show that the protein recognizes and binds mannose and N-acetylglucosamine residues almost indiscriminately at the same binding site. Physical and chemical studies suggest the intact binding protein with an approximate molecular weight of 194,000 to be composed of six identical subunits. The protein is characterized as a glycine-rich protein. The apparent ubiquitous distribution of mannan-binding protein in mammalian liver is consistent with the proposal that the binding protein is the cellular receptor mediating the hepatic uptake of glycoproteins terminated with mannose and/or N-acetylglucosamine residues.