Conditioned media obtained from fibroblasts cultured from rheumatoid and certain other inflammatory synovia were observed to stimulate [3H] thymidine incorporation in an indicator murine fibroblast line. Synovial fibroblasts derived from thejoints of patients with osteoarthritis did not display this property. This effect persisted in culture for many weeks and occurred in the absence of co-stimulatory immune cells. Antibody neutralization studies implicated a role for basic fibroblast growth factor (bFGF), transforming growth factor Q (TGF-a), granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin 10 (IL1) 3) in the increased proliferative activity of synovial fibroblast-conditioned media. Synovial cell synthesis of bFGF, TGFa1, GM-CSF, IL10, and 11, 6 was confirmed by 31S-methionine labeling and immunoprecipitation. The constitutive production of inflammatory and mitogenic cytokiries by synovial fibroblasts may represent the result oflong-term, phenotypic changes that occurred in vivo. Persistent cytokine production by synovial fibroblasts may play an important role in the continued recruitment and activation ofinflammatory cells in chronic arthritis and in the formation of rheumatoid pannus.