From July 1984 to December 1987, 9 patients with lupus nephritis did not respond to the administration of two courses of methylprednisolone pulse therapy and cyclophosphamide treatment for 56 days. Therefore, high-dose intravenous human gamma-globulin (IVIG) was administrated. Before IVIG therapy, renal biopsy showed class IV lupus nephritis in 5 cases, class V in 2 cases, and class IV with V in 2 cases. Immunofluorescence of the renal biopsy showed heavy IgG deposits along the glomerular capillary walls. These heavy glomerular IgG deposits were dissociated after in vitro incubation of the cryostat kidney sections with plasmin-treated, PEG-treated, sulfonated human gamma-globulin and a human Fc fragment, as evidenced by a dramatic decrease or even absence of fluorescent intensity. After high-dose IVIG treatment, 3 out of 5 cases of class IV lupus nephritis had a good response with decreased proteinuria and creatinine; serum C3, C4 levels and CH50 hemolytic activity also increased. The glomerular IgG deposits decreased in the follow-up biopsy. Pathologically, 2 of them transformed into class IIb. The capacity to synthesize immunoglobulin after pokeweed mitogen stimulation was reduced and the circulating immune complexes (CIC) lowered after high-dose IVIG treatment. In the others there was partial response. These clinical and immunological improvements after high-dose IVIG therapy are probably related to the modulation of macrophage-T cell function and enhancement of suppressor T cell function. The toxicity of high dose IVIG was minimal, but the cost is high, search for an optimal dosage is warranted.