β<sub>2</sub>-Microglobulin (B2M) is the amyloid preprotein that accumulates in amyloid osteoarthropathy associated with hemodialysis. To elucidate the mechanism of such amyloidogenesis, we investigated the interaction between B2M and collagen in vitro by solid-phase enzyme immunoassay. Soluble collagens which had been solidified on plastic plates were allowed to react sequentially with B2M, peroxidase-conjugated antibody to B2M, and the substrate. The collagen-binding activity was dependent on the concentration of B2M and collagen, respectively. These results suggest that the collagen-binding affinity of B2M plays an important role in amyloidogenesis.