Background: A constant finding in β<sub>2</sub>-microglobulin (β2m) amyloidosis is an increase in tissue heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PGs) at sites of amyloid deposits. However, the binding characteristics of PGs with β2m have not been elucidated yet. Methods: Using affinity retardation chromatography, β2m- and glycosaminoglycan (GAG)-anchored columns, an affinity between β2m and GAGs was analyzed. Five peptides which spanned the entire β2m amino acid sequence were prepared, and an affinity between these peptides and heparin (HP) was examined. Furthermore, the specific binding of biotinylated β2m peptide for AA amyloid deposits via GAGs was examined on tissue sections. Results: Using β2m-anchored column, HP showed the smallest dissociation constant (K<sub>d</sub>), i.e. the strongest affinity, among the GAGs examined. At 0.4 M NaCl, the K<sub>d</sub>s of β2m relative to BSA-anchored columns for HP, HS, CS-A, CS-B, and CS-C were 94, 620, 130, 660 and 190 µ M, respectively. Using GAG-anchored columns, at 0.15 M NaCl, pH 7.4, β2m also showed an affinity for HP, with the K<sub>d</sub> relative to a reference column being 370 µ M. Under the latter conditions, no β2m affinity for CSA was demonstrated. Among the five peptides, peptide-1, which is composed of residues 1–24, showed the highest affinity for HP, the K<sub>d</sub> being 190 µ M. Peptides analogous to peptide-1, in which each basic amino acid was individually replaced by alanine, showed a remarkable decrease in affinity for HP. The specific binding of biotinylated β2m peptide for AA amyloid deposits via HS and CS was confirmed in situ by pretreatment with heparitinase and chondroitinase ABC. Conclusion: The present data indicate that HP/HS is effective in the binding of the β2m monomer, and the anatomic localization of β2m amyloid precursor protein.