Highly purified human serum glycoproteins were treated with neuraminidase and examined for their cross reaction with several lectins with anti-galactosyl specificity: beta-D-galactosyl structures are thought to be the main terminal sugar residues that become attached de novo after removal of neuraminic acid. The following lectins were tested: Tridacnin from the bivalve clams Tridacna maxima and Tridacna gigas, the agglutinin from the sponge Axinella polypoides, the lectin from the roach Rutilus rutilus and the plant lectins from Ricinus communis, Ononis spinosa, Glycine soja and Abrus precatorius. In agar gel diffusion, these purified and precipitating lectins gave more or less strong or negative results against the different neuraminidase-treated serum glycoproteins, thus indicating subtle differences with respect to their anti-galactosyl combining specificity. On the other hand, serum glycoproteins which reacted with the same lectin, did not always show complete identity lines. Finally, as revealed by these lectins, the carbohydrate moiety of serum glycoproteins may reflect a complex and broad spectrum of heterogeneity. This could lead to a more detailed understanding of the topographical and steric arrangement of the chemical structure and of the biological role of carbohydrate groups in these glycosubstances.