We conducted a preliminary study of monthly intravenous cyclophosphamide (IVCY) therapy on children with active lupus nephritis to evaluate the clinical efficacy and safety of IVCY pulse therapy. From June 1993 to May 1994, 13 patients (mean age: 14 +/- 0.9 years old; female: male = 11:2) with active lupus nephritis were treated with intermittent IVCY in addition to their regular corticosteroid therapy. Criteria for patients who received intermittent IVCY therapy were associated with any one of the following conditions: 1) with renal biopsy-proved diffuse proliferative glomerulonephritis; 2) with nephrotic syndrome and are inert to high dose of prednisolone therapy; and 3) with severe side effect of steroid therapy. Cyclophosphamide (CY) was administrated monthly for the first 6 doses, and at 2 to 3-month interval afterward for 2 years. The mean IVCY pulses per patient was 6.5 +/- 0.5 times. The initial dose of CY was 0.5 gm/mm2, then gradually increased to 1 gm/mm2 with a monthly increment of 0.25 gm/mm2. After 6 months, cyclophosphamide treatment was associated with significant improvement in mean levels of serum C3 (41.6 +/- 5.1 vs. 96.7 +/- 11.3 mg/dl), C4 (11.7 +/- 1.1 vs. 35.3 +/- 5.0 mg/dl) and anti-DNA titer (65.4 +/- 17.1 vs. 9.1 +/- 2.8 IU/ml) (all p < 0.01), despite a significant reduction in mean prednisolone dosage (48.5 +/- 4.8 vs. 15.6 +/- 3.2 mg/day; p < 0.01). The mean creatinine clearance also improved significantly from 44.7 +/- 5.7 to 81.9 +/- 2.7 ml/min/1.73 mm2 (p < 0.01) after 6 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)