AbstractCartilage‐synovium interactions were explored in a model culture system. Bovine nasal‐cartilage discs were cocultured with minced rheumatoid synovium or synovium‐conditioned media (SCM) in the presence or absence of hydrocortisone. Cartilage breakdown was assessed by the release of proteoglycan (PG) and hydroxyproline, and matrix biosynthesis by [35S]sulfate incorporation during pulse labeling. Chondrocyte‐dependent breakdown in response to synovial factors (i.e., “catabolin” activity) was assessed by the difference in PG release between living and dead cartilages. Short‐term contact with minced synovial membrane or exposure to its products released at a distance was sufficient to induce cartilage degradation in coculture; continued exposure was not required for breakdown to persist. Conditioned media from short‐term synovial culture were similarly potent, and the induced breakdown was chondrocyte dependent. Matrix biosynthesis was inhibited in exposed cartilage but could be rapidly restored to normal on synovium removal despite the persistence of cartilage breakdown. Early hydrocortisone treatment suppressed the initiation of cartilage breakdown in cocultures and largely abolished the appearance of inductive factors in SCM. Later applications had little effect either in cocultures or in catabolin assays. We conclude that synovium‐induced breakdown is an early event and that chondrocyte catabolic mechanisms once they have been activated are sufficient to maintain breakdown at a high level. Hydrocortisone, as well as limiting proteolysis, inhibits early tissue interactions at the level of synovial catabolin prod