Recent data are presented which indicate a critical role for interleukin ( IL)- 18 in rheumatoid arthritis ( RA). The T cells and macrophages invading the synovium or in the synovial fluid are the chief cellular targets of IL- 18 in RA. Neutrophils, dendritic cells and endothelial cells may also be cellular mediators of IL-18. The direct effect of IL- 18 on fibroblast- like synoviocytes or chondrocytes may not be essential or important. In RA, IL- 18, which is mainly produced by macrophages, activates T cells and macrophages to produce proinflammatory cytokines, chemokines, adhesion molecules and RANKL which, in turn, perpetuate chronic inflammation and induce bone and cartilage destruction.