Bovine serum albumin (BSA) glomerulonephritis is a type of immune complex glomerulonephritis that is characterized by a large number of leukocytes infiltrating the kidney. Interleukin (IL)-18, which has potent interferon (IFN)-gamma-inducing activities, may play an important role in lymphocyte-mediated inflammatory responses. To investigate the role of IL-18 in BSA glomerulonephritis, we used IL-18R-deficient C57BL/6 mice. Compared with control mice, IL-18R-deficient mice showed a significant reduction of proteinuria, renal pathological findings including glomerular IgG and C3 deposits, and leukocyte infiltrates. Transcripts encoding IFN-gamma and tumor necrosis factor (TNF)-alpha in the kidney were significantly reduced in IL-18R-deficient mice compared with those in control mice. On the other hand, serum anti-BSA Ab was not reduced in IL-18R-deficient mice. We conclude that the blockading of IL-18 signaling in BSA nephritis mice significantly alleviates immune complex renal disorder; this may thus represent a novel approach to the treatment of patients with immune complex nephritis.