Steroid-resistant FSGS and its recurrence posttransplantation are predominantly seen in children. We report on the largest pediatric transplant population for FSGS with similar numbers of azathioprine- and cyclosporine-treated patients analyzed for recurrence. Of 70 patients with idiopathic FSGS identified over the years 1974-1989, 49 progressed to end-stage renal disease and 28 received 42 transplants (17 live-related donors, 25 cadaveric). Seventeen patients each received one transplant, 9 patients each received two transplants, and one patient each received three and four transplants. The mean age at diagnosis of FSGS was 9.1 +/- 4.2 years, the mean duration of FSGS prior to reaching ESRD was 2.2 +/- 1.3 years, and the mean duration on dialysis prior to transplantation was 9.7 +/- 6.3 months. Primary nonfunction was observed in 2 transplants; in the remaining 40 transplants, 6 recurrences were noted (15%). Recurrences were noted in four AZA and prednisone (n = 22) and two CsA and prednisone (n = 18) recipients. Risk factors analyzed for recurrence included race, age at FSGS, histological and clinical severity of FSGS, classification of FSGS, duration of disease, interval on dialysis, multiple transplants, and HLA matching. Only age at onset of FSGS was predictive of recurrence. The incidence of recurrence was higher in children less than or equal to 6 years of age compared with those over 6 years (P less than .05). All 4 patients receiving AZA and prednisone went on to lose their grafts due to recurrence. Recurrent proteinuria in the 2 CsA and prednisone recipients was controlled by gradually increasing the CsA dose from 15 mg/kg/day to 27 and 35 mg/kg/day. Remission of the nephrotic syndrome was induced within 60 days in both patients. Presently, both grafts are functioning 24 and 16 months posttransplant with serum creatinines of 0.9 and 0.5 mg/dl, respectively. We conclude that recurrence is predominantly seen in very young children and occurs even under CsA immunosuppression. High-dose CsA may control the recurrent proteinuria--however, the long-term outcome of such intense therapy is not known.