Despite its widespread use, there are only a few published studies of the use of intravenous high-dose pulse cyclophosphamide in lupus nephritis in children. There are few data about the long-term efficacy and safety of this form of therapy. This study evaluates the clinical efficacy of this regimen in children with severe lupus nephritis followed prospectively over a 5-year period. Nine children with severe active lupus nephritis were enrolled in a treatment regimen of monthly intravenous pulses of cyclophosphamide (0.75-1 g/m(2)) for 6 months and then every 3 months for a total of 36 months. Cyclophosphamide treatment was associated with significant improvement in renal function during treatment. However, data presented here show that 56% of the patients progressed to chronic renal failure and 22% required dialysis 2 years after discontinuation of cyclophosphamide therapy. Hence it seems that this regimen is not effective in our patients in the long term, especially patients who present with high serum creatinine and hypertension.