It is likely that a complex bidirectional interaction occurs between mesangial cells and the immune cells which infiltrate the mesangium during nephritis. Macrophages and other immune cells liberate a series of mediators, including substances such as IL-1, beta-endorphin, TNF, and PDGF--all of which promote the growth of mesangial cells. The end result is mesangial cell proliferation and increased matrix production, both of which are seen in nephritis. The proliferating mesangial cells liberate autocoids such as IL-1 and PDGF, thereby setting up an amplifying loop. Simultaneously, suppressive factors such as TGF-beta are released which antagonize the actions of these growth-promoting substances. The proliferating mesangial cells also produce immunomodulatory peptides, which will in turn act on the infiltrating macrophages to stimulate their replication and activation. Such activated macrophages continue to amplify the inflammatory lesion and also promote the phagocytosis of localized antigen-antibody complexes. The net effect of all of these interactions will depend on the dominance of substances which persist and override the roles of other molecules. Studies of the controls which regulate the production of these growth factors/immune modulators will yield insights into the fundamental mechanisms which determine the outcome in glomerulonephritis.