Development of steroid dependency represents a significant therapeutic challenge in steroid-sensitive nephrotic syndrome. Previous studies have shown conflicting results concerning the benefit of a 12-week treatment with cyclophosphamide (CPO), with 24%-67% of patients achieving long-term remission. We therefore analyzed the clinical response of 20 consecutive children with steroid-dependent nephrotic syndrome (SDNS) (12 male, median age at start of treatment 5.9 years, range 3.2-14.7 years) treated at our institution with CPO (2 mg/kg per day) for 12 weeks since 1989. Median duration of follow-up was 5.8 (range 1.1-9.25) years. Only 6 of 20 children (30%) showed a long-term remission of >2 years, while 14 of 20 (70%) developed relapses again. Of these, 12 patients (86%) again developed steroid dependency, requiring further alternative treatment. Our data show that a 12-week course of CPO leads to unfavorable results in the majority of patients with SDNS. We therefore conclude that there is a need for further optimization of therapy in SDNS.