Although the pathogenesis has yet to be fully understood, β2-microglobulin (β2m) related amyloidosis is a frequent complication in long-term hemodialysis (HD) patients. In an attempt to clarify the association of two potential candidates with amyloidogenesis from β2m in HD patients, human urine-derived β2m solution alone or combined with glycosaminoglycans: hyaluronic acid, heparan sulfate, or serum amyloid P component (SAP) were dialyzed against physiological buffered solution (pH 7.4) using a microdialyzer in vitro for 72 h at 4°C. This study demonstrates for the first time that SAP can play a crucial role in the formation of amyloid-like fibrils from β2m. This occurs by a direct influence on either the processing of a precursor protein, or protein folding, in vitro, by a short-period dialysis against a physiological buffered sol