A human cold agglutinin (McC) has been isolated from the serum of a patient with Waldenström's macroglobulinemia by affinity chromatography with a column of glutaraldehyde-fixed erythrocyte stroma mixed with celite. The agglutinin, which is an IgM κ, reacts weakly with normal adult erythrocytes and strongly with cord cells as well as with adult Oh and Ol cells. The reactivity of all cell types tested was increased to approximately the same level by treatment of the cells with ficin. Inhibition studies indicate the agglutinin is specific for the nonreducing terminal carbohydrate sequence Galβ1-4GlcNAcβ1-3Gal….