Primary focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and eventual end-stage renal disease. It is known to be due to an abnormality of the visceral epithelial cells (podocytes) of the glomerulus. The morphological hallmark of primary FSGS is diffuse effacement of podocyte foot processes. The etiology of the podocyte damage is not been clearly established. FSGS can also be a secondary process due to underlying conditions including obesity and heroin use. In the secondary processes, the mechanism appears to be a decreased ratio of podocytes to the glomerular filtration surface area. Familial forms of FSGS also exist due to alterations of several different podocyte proteins. Primary FSGS is an increasing cause of end-stage renal disease. Recurrence of severe FSGS in renal allograft recipients presents a major challenge to transplant physicians. The incidence of recurrence is generally accepted to be between 20% and 30%. Risk factors for and characteristics of recurrence include a rapid progression of the primary disease to end-stage renal failure, early onset of nephrotic range proteinuria after allografting, frequent loss of the allograft, a high frequency of recurrence in subsequent allografts, and children less than 15 years of age. Some investigators have identified a circulating factor called the FSGS factor that appears to be associated with recurrence after transplantation. This factor has been shown to be a protein between 30 and 50 kd molecular weight. Logically, the possibility of a circulating factor associated with recurrence of FSGS led investigators to treat patients with plasmapheresis. Several studies have been reported with varying success. The response of patients to plasmapheresis seems to be completely individual. Other studies have added cyclophosphamide and/or mycophenolate mofetil to the plasmapheresis protocol. Again success in these studies has been variable. However, because some patients show complete recovery with plasmapheresis, individuals who develop recurrent FSGS after transplantation usually are given a trial of plasmapheresis therapy.