Patients with steroid-resistant nephrotic syndrome often have an unsatisfactory long-term outcome and are at risk of developing chronic renal failure. We prospectively treated 65 children with idiopathic steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis (FSGS) with intravenous pulses of corticosteroids and oral cyclophosphamide. Dexamethasone (5 mg/kg) or methylprednisolone (30 mg/kg) was administered intravenously, initially 6 pulses on alternate days, followed by 4 fortnightly and 8 monthly pulses. Oral cyclophosphamide therapy was given for 12 weeks and tapering doses of prednisolone were administered for 52 weeks. The mean age at treatment was 85.7+/- 44.9 months. Five patients developed serious infections during administration of initial alternate-day pulses and were excluded. Of 59 patients who completed initial alternate-day therapy, 17 had complete and 8 partial remission; 34 (57.6%) patients did not respond to treatment. The median urine protein to creatinine ratio decreased from 10.0 to 0.75 (P<0.005) and serum albumin increased from 1.9 g/dl to 2.4 g/dl (P<0.01). The median duration of follow-up after stopping pulse therapy was 25.6 months. Thirty-four patients were followed for more than 3 years (median 4.5 years). Of these, 22 (64.7%) patients had a favorable outcome; persistent complete remission was seen in 15 patients and steroid-responsive relapses in 7. Seven patients had non- nephrotic-range proteinuria, 2 had nephrotic-range proteinuria, and 3 (8.8%) were in chronic renal failure. There was no significant difference in the short- and long-term outcome of patients with initial (n=28) and late resistance (n=31). The outcome in patients receiving intravenous dexamethasone (n=48) or methylprednisolone (n=11) was also similar. The chief side effects included worsening of height standard deviation score (47.4%), transient hypertension (42.5%), and serious infections (18.5%). We conclude that prolonged treatment with intravenous corticosteroids and oral cyclophosphamide is beneficial in patients with steroid-resistant FSGS. Expensive protocols can be successfully modified and used, depending upon the availability of health resources.