The production of large amounts of NO in vitro by cytokine-activated chondrocytes has been established. In vitro studies suggest that NO compromises chondrocyte survival. The role of NO in regulating matrix biosynthesis and degradation has received much attention. Most studies indicate that NO is at least partly responsible for IL-1-induced suppression of glycosaminoglycan and collagen synthesis. NO also may be involved as a mediator of IL-1-induced expression of MMP, mRNA, and protein and may contribute as an activator of the latent forms of the enzymes. Although the interaction of NO and prostaglandins is of considerable interest, current data are inconclusive with respect to the role of NO in the regulation of prostaglandin synthesis, although it seems clear that prostaglandin is not involved in NO synthesis. It is important to note that NO does have protective effects in cartilage and other tissues. Under certain conditions, NO may have anabolic and anticatabolic effects in cartilage. In other tissues, notably in skin and muscle, NO has been found to have a stimulatory role in extracellular matrix repair. In antimicrobial defense, in general, and in bacterial arthritis specifically, NO is an important protective molecule. Production of NO in arthritis-affected cartilage and synovium is a consistent feature of human and experimentally induced arthritis. The production of NO is associated with matrix degradation and chondrocyte apoptosis. The administration of NO synthase inhibitors in experimentally induced arthritis has resulted in reduction of synovial inflammation and destruction of cartilage and bone.