The proliferation of rabbit synovial cells, 3T3 cells, or simian virus-transformed 3T3 cells in cell culture was inhibited by the addition of hyaluronate to the culture medium. This effect was markedly dependent on the molecular weight and concentration of the hyaluronate. At the molecular weight and concentration of hyaluronate present in normal synovial fluid, proliferation was inhibited. At lower molecular weights or concentrations, as found in rheumatoid synovial fluid, hyaluronate was significantly less inhibitory. Thus, the changes in synovial fluid hyaluronate that are associated with arthropathies may contribute to a favorable environment for rheumatoid pannus expansion.