beta 2-microglobulin-related amyloidosis (A beta 2M), in long-term dialysis patients, is a new and frequent complication for which the pathogenesis remains unknown. The authors documented, by light and high resolution electron microscopy, the spontaneous polymerization of beta 2-microglobulin to amyloid fibrils in mononuclear cell culture supernatants from dialysis patients. These data provide significant information about the pathogenesis of dialysis-amyloidosis, revealing an unusual and different fibrillogenic mechanism for beta 2-microglobulin and dialysis-amyloidosis than for other forms of amyloidosis. beta 2-microglobulin does not appear to require a proteolytic process before polymerization into amyloid fibrils and deposits. This study represents the first cell culture system in which beta 2-microglobulin amyloid fibrils have been spontaneously created.