Forty consecutive patients whose biopsies showed focal and segmental sclerosis were studied for 6 to 16 years to establish the long-term prognosis of this group of patients. By the end of a decade 21 were dead, on regular dialysis or transplanted; only one death was unrelated to renal failure. A further 8 patients had a GFR of less than 60 ml/min/1.73 m2. Only 11 patients had normal renal function, and of these eleven only four had no urinary abnormality. Actuarially calculated survival was 75% at 5 years, 50% at 10 years, and 38% at 15 years. There was no difference between the 28 adults and the 12 children in terms of evolution. Patients with a nephrotic syndrome at presentation had a poorer prognosis than those never nephrotic. Twenty nephrotic patients were treated with prednisone, and 14 of these with cyclophosphamide in addition. One patient responded with loss of proteinuria within two months to both drugs, and another lost proteinuria when treated with cyclophosphamide. Thirteen patients received allografted kidneys; a nephrotic syndrome recurred in three patients, with histological evidence of recurrent disease in two.