The overall objective of this proposal is to elucidate the pathogenic mechanisms of cartilage damage in human arthritis. It is proposed to study 1) the interactions of cartilage chondrocytes with anti-collagen antibodies present in a proportion of synovial fluids of patients with rheumatoid arthritis, and their effects on chondrocyte function; 2) the role of oxidative processes mediated by inflammatory cells in synovial fluids on the generation of noxious lipids peroxides and modified immunoglobulins, and their effects on chondrocytes, polymorphonuclear leukocytes and monocytes. These studies will involve the use of a variety of biochemical and immunochemical techniques.