Renal transplantation is considered to be the treatment of choice of dialysis-related beta 2-microglobulin amyloidosis (DRA), as it provides near-normal serum levels of beta 2-microglobulin and obviates the need for dialysis. However, the long-term outcome of DRA after transplantation has not been fully assessed, and its evolution after transplant failure has not been reported. This study examined 17 patients with histologically confirmed DRA who underwent kidney transplantation and had a dialysis-free follow-up period in excess of 1 yr. Immunosuppressive treatment included low-dose prednisolone, cyclosporine, and/or azathioprine. Symptoms related to DRA were sought at every outpatient visit, and bone x-rays were performed at time of transplantation and annually thereafter. The number and size of the bone cysts were determined. Most of the DRA symptoms, and particularly shoulder stiffness, disappeared within the first wk after transplantation and this persisted throughout the transplant follow-up period (58.5 +/- 9 months). However, the number of bone cysts remained remarkably constant even in those patients with still-functioning grafts (12 +/- 7.5 and 12.1 +/- 7.7, before and at last transplantation follow-up examination, respectively). Beta 2-microglobulin amyloid was found to be present in one patient operated on for hip fracture 2 yr after receiving a well-functioning transplant. Seven patients experienced graft failure and returned to dialysis after 47 +/- 39 months of transplantation. Severe DRA symptoms reappeared strikingly early after resuming hemodialysis, and five out of the seven patients required surgery for carpal tunnel syndrome, three of them within the first yr (mean, 17 +/- 12 months). The number of cysts significantly increased from 17 +/- 11 to 21 +/- 11 during the second dialysis period. These findings provide further evidence suggesting that although the clinical expression of DRA is arrested during transplantation, the anatomical lesions and the pathological processes underlying it are unlikely to be reversed.