Although immunosuppressive regimens of corticosteroids combined with high-dose intravenous cyclophosphamide (IVCY) have been reported to suppress the activity of lupus nephritis, there is controversy regarding its application for children and adolescents, because of its potential toxicity including gonadal dysfunction. On the basis of the recent finding that a low-dose IVCY regimen for induction therapy in adult lupus nephritis effectively achieves renal remission comparable with that achieved with a conventional high-dose IVCY regimen, we treated two children with severe lupus nephritis by low-dose (fixed dose of 500 mg m(-2), cumulative dose 3 g m(-2), approximately one-fourth of the conventional high-dose IVCY regimen) IVCY and oral mizoribine (5 mg kg(-1) day(-1)) and steroids (3 methylprednisolone pulse followed by oral prednisolone). They responded well to this regimen, showing remarkable improvement in both histological and clinical manifestations in a short period of time. From these findings we suggest that the new low-dose IVCY regimen may be as effective as the conventional high-dose IVCY regimen, without significant adverse effect, for induction therapy in children with severe lupus nephritis (class III or IV).