A serum lectin specific for mannose and N-acetylglucosamine residues was isolated from human serum to near homogeneity mainly by affinity chromatography on a column of Sepharose 4B-mannan. The lectin, called mannan-binding protein, was a glycine-rich protein with an apparent molecular size of approximately 600, 000 daltons, and had a subunit structure consisting of a single component with an apparent molecular weight of 31, 000. Binding of the isolated lectin to ¹²⁵I-labeled mannan was dependent upon the presence of Ca²⁺, proportional to the protein added, and a reversible and saturable process. Scatchard plot analysis of binding data indicated the presence of a binding site with a dissociation constant of 2.3×10^-9M and a maximum capacity of 4.3 pmol of ¹²⁵I-labeled mannan per Fig of protein (2.6 mol of mannan per mol of the protein). The mannan-binding protein, is different from C-reactive protein (CRP) and amyloid P-component (SAP), both of which are serum components known to bind polysaccharides in the presence of Ca²⁺. A distinct binding activity toward mannan which did not require Ca²⁺ was attributed to immunoglobulins (IgG).