We investigated the role of insulin-like growth factors (IGFs) as regulating factors of cartilage metabolism in human synovial fluid (SF), using a bovine explant culture system that was shown to respond to recombinant IGF-1 in vitro. SF from rheumatoid arthritis (RA) patients and from control patients was found to stimulate chondrocyte proteoglycan synthesis in bovine articular cartilage. A monoclonal antibody directed primarily against IGF-1 (and to some extent, IGF-2) partially blocked the stimulatory action of serum and totally blocked the stimulation by SF. These findings indicate that IGFs are major regulating factors of cartilage proteoglycan synthesis in human SF. In addition, we measured serum and SF levels of IGF-1 in RA patients and control patients, using a radioimmunoassay. No difference in immunoreactive serum IGF-1 was detected between patients and controls. The IGF-1 levels in SF were consistently lower than in serum, for both patient groups. No differences in IGF-1 concentration were found between RA and non-RA SF. The relevance of these data with respect to joint inflammation is discussed.