We prospectively evaluated the efficacy and safety of a 24-month course of intermittent intravenous cyclophosphamide (IC) therapy for children suffering from lupus nephritis soon after the diagnosis of systemic lupus erythematosus (SLE) was made. Eight children with severe lupus nephritis were treated with IC monthly for 6 months and then every 3 months, totaling 24 months. The repeated measurements of sequential serological parameters of lupus nephritis, monitored over the course of the study, were analyzed statistically. The urine creatinine clearance rate (Ccr), the 24-h urine protein excretion, and the serum creatinine level significantly improved (p<0.05) after 6, 9 and 12 months of treatment, respectively. The serum C3, C4, albumin, and triglyceride level, the hemoglobin level, and the erythrocyte sedimentation rate significantly improved (p<0.05) 1 month after treatment. The IC appeared to elicit a significant effect (p<0.05) upon the mean leukocyte and neutrophil counts but had no effect (p>0.05) on the platelet count. The lymphocyte count decreased (p<0.05) during the first six monthly IC, whereas the lymphocyte count returned to the baseline level during the quarterly IC events. From a total of 96 IC doses given to those SLE patients, severe myelotoxicity occurred in one patient when lymphocyte count declined to 98 mm(-3); however, no sign of clinical infection was observed. The daily steroid dosage can be tapered rapidly, and the SLE-associated hyperlipidemia resolved parallel to the resolution of the acute lupus nephritis. We concluded that the efficacy of a 24-month IC course for a child suffering from lupus nephritis is significant.