Lupus nephritis results from an acute inflammatory and immunological response to renal immune complex deposition. The acute response is characterized by activation of circulating leukocytes and renal parenchymal cells, triggering the production of pro-inflammatory cytokines and growth factors. In all too many cases, this response is followed by a chronic response, which is characterized by excessive deposition of collagen and other extracellular matrix macromolecules and the development of end-stage renal disease. Mechanisms underlying this chronic response in progressive renal disease are not adequately defined. In this overview, potential roles of reactive oxygen species (ROS) generation and transforming growth factor-beta (TGF-beta) production in the pathogenesis of lupus nephritis are considered. ROS and TGF-beta may be key elements of a pathway leading to persistent and excessive matrix deposition in progressive lupus nephritis. Further studies to define the role of this pathway in lupus nephritis may lead to the development of additional, more specific therapeutic targets to prevent progression of renal disease.