The evidence supporting a role for TNF-alpha in glomerular diseases can be summarized with the following: TNF-alpha can be secreted in the kidney by intrinsic renal cells and infiltrating phagocytes, as has been shown in vitro and in vivo during glomerular injury. TNF-alpha has proinflammatory actions which include cell death, chemotactic properties, and modulation of secretion of other inflammatory mediators, and extracellular matrix (Fig 5). Administration of exogenous TNF-alpha or agents that induce release of endogenous TNF alpha, such as endotoxin, increase the severity of experimental glomerular injury. Furthermore, the blockade of TNF-alpha action with specific antibodies, soluble receptors, or inhibitors improves the outcome of glomerulonephritis. Finally, several of the agents currently in use for the therapy of glomerular injury, such as corticosteroids and cyclosporine, are known to modulate the production of TNF-alpha. Specific TNF-alpha antagonists or inhibitors may have a role in the management of glomerulonephritis in the future.