Recent advances in basic research on the immune system and molecular biology of cartilage components have greatly increased our understanding of the role of autoimmunity in inflammatory diseases affecting joints, particularly rheumatoid arthritis. Many of these diseases are common and their complex pathogenesis probably involves a large number of genes polymorphic in the population as well as environmental factors. Characteristic features of inflammatory arthritis include expansion of the synovial tissue into a pannus containing lymphocytes and macrophages, autoimmune reactions against cartilage antigens, and erosion of cartilage. Since hyaline cartilage of the articular surfaces is the only structure within the joint known to contain joint-specific antigens this tissue is the prime suspect as the target of the autoimmune This review will first present the capacity of the immune system to discriminate between self and non-self structures, and then summarize our current understanding of the structures of cartilage collagens. Subsequently we will discuss how the immune system normally interacts with cartilage and how such interactions can lead to arthritis. We propose that collagen-induced arthritis (CIA) is valuable for understanding the autoimmune recognition of cartilage collagen which precedes the outbreak of arthritis and may perpetuate its chronicity, and serves as an animal model of rheumatoid arthritis.