Lupus nephritis (LN) is characterized by an increased upregulation of Th1. This study was undertaken to evaluate the role of CD134 in cytokine production in peripheral blood mononuclear cells (PBMCs) from subjects with LN. Percentages of IFN-gamma- (Th1), IL-4-, and IL-10- (Th2) producing cells within the PBMC CD4+ T cell population of LN subjects were found to be higher than those of healthy subjects. Stimulation of PBMC from LN subjects with anti-CD3 epsilon mAb/rIL-2 resulted in further increases in cytokine production. Stimulation in the presence of anti-CD134 mAb resulted in reduced IL-4 and IL-10 production; however, it also resulted in increased IFN-gamma production. Stimulation in the presence of the fusion protein rhCD134:Fc resulted in decreased production of all three cytokines. The possibilities that anti-CD134 therapy may control the extent of IL-4- and IL-10-mediated damage in active LN and that rhCD134:Fc therapy may prevent occurrence of LN are discussed.