In T cell-mediated autoimmune diseases such as rheumatoid arthritis, Th1 cells and their cytokines, especially interferon-gamma (IFN-gamma), are responsible for the induction and persistence of chronic inflammation and tissue destruction. But emerging evidence from experimental models has demonstrated that IFN-gamma also possesses unexpected anti inflammatory properties. The recent data discussed in this article indicate that beside the well-known proinflammatory efficacy, IFN-gamma may function as a master regulator of inflammation and immune responses. Such self-regulatory processes seem to play an important role in the inhibition of excessive responses and to maintain or reestablish homeostasis of the immune system.