From January 1986 to December 1988, 8 patients with lupus nephritis did not respond to the administration of two courses of methylprednisolone pulse therapy and cyclophosphamide treatment for 56 days. These cases then received intravenous prostaglandin E<sub>1</sub> (PGE<sub>1</sub>) for 3 weeks. All of them had a good response with decreased proteinuria and azotemia; serum C3 and C4 levels and creatinine clearance also increased. Both OKT4<sup>+</sup> and OKT8<sup>+</sup> cells increased, and the OKT4/OKT8 ratio was almost normal. The macrophage functions included increased production of interleukin 1 and γ-interferon. The capacity to synthesize immunoglobulin after pokeweed mitogen stimulation was reduced, the circulating immune complexes lowered, and glomerular IgG deposits decreased in the two class IV follow-up biopsy cases after PGE<sub>1</sub> therapy. These clinical improvements after PGE<sub>1</sub> therapy are probably related to the modulation of macrophage T-B cell interaction, enhancement of reticuloendothelial system function, and increased glomerular capillary flow.