We review our experience with low-dose intravenous pulse cyclophosphamide as treatment of biopsy-proven lupus nephritis. Seventeen patients were treated with 2-4 (mostly 3) weekly low-dose intravenous pulses of cyclophosphamide (500 mg) and moderate doses of prednisolone (0.5 mg/kg/day), followed by an oral immunosuppressive drug (either azathioprine or cyclophosphamide). As compared with the classical monthly high-dose cyclophosphamide regimen, this weekly low-dose regimen induced neutropenia in one patient only. The incidence of herpes zoster was very low (6%). At the end of the follow-up period (15 +/- 8 months), two patients required chronic ambulatory peritoneal dialysis. The 14 patients that could be evaluated improved their mean serum albumin from 30 +/- 7 to 37.5 +/- 7 g/l (mean +/- SD; P < 0.01) and their mean serum creatinine fell from 125 +/- 119 to 101 +/- 66 mumol/l (not significant). Mean DNA binding dropped from 71 +/- 29 to 26 +/- 27% (P < 0.001) and mean complement fraction C4 levels increased from 14 +/- 8 to 28 +/- 18 mg/dl (P < 0.05). The mean daily prednisolone dose was dramatically reduced from 26 +/- 8 to 10 +/- 4 mg (P < 0.001). Although this preliminary and retrospective study clearly needs validation with a larger cohort followed for a longer period, it seems that a treatment combining moderate doses of steroids and 3-4 weekly low-dose intravenous pulses of cyclophosphamide, followed by oral immunosuppression, is well tolerated and beneficial--at least in the short term--for most patients with severe lupus nephritis.