We studied the long-term outcome of a group of children with the nephrotic syndrome who showed the histological lesion of focal segmental glomerular sclerosis (FSGS) during the course of their illness. Of 25 such children studied, a complete follow-up ranging from 3 to 19 years was available in 24. Two distinct groups could be identified. Patients in the first group were characterized by steroid resistance (SR) from the onset, whereas those in the second group were initially steroid sensitive (SS), and had the histological lesion of minimal change which, over time, evolved into FSGS. SR patients had a mean age of 7.7 ± 3.7 years compared to SS patients who were 3.5 ± 2.5 years old (p < 0.01). There were more females (11 of 14) in the SR group than in the SS group (3 of 10; p < 0.02). The incidence of hematuria was higher in the SR patients (9 of 14) than SS patients (2 of 10; p < 0.05). SR patients also exhibited a greater degree of growth retardation at the end of the follow-up period (9 of 13 compared to 1 of 8 SS patients; p < 0.02). SR patients reached end-stage renal failure earlier (2.3 ± 1.3 years) than SS patients (10 ± 5.8 years; p < 0.01) after the initial biopsy. Of the 13 kidneys transplanted into 9 SR patients, recurrence of FSGS was noted in two allografts. Of the 4 kidneys transplanted into 2 SS patients, recurrence was seen in 1. The overall recurrence rate of FSGS in allografts was 17.6%. Our study suggests that the two varieties of FSGS occurring in nephrotic patients may be distinct nosologic entities rather than a single disease with varied manifestations.