Transforming growth factor beta (TGF beta) is a multipotent regulator of cell proliferation and extracellular matrix synthesis. In our study we show that the effect of TGF beta on proliferation and proteoglycan synthesis of articular cartilage chondrocytes appears to be dependent on the period in culture of these chondrocytes. TGF beta inhibits DNA and proteoglycan synthesis of freshly isolated chondrocytes while the DNA and proteoglycan synthesis of chondrocytes cultured in monolayer was stimulated by TGF beta. Since TGF beta is present in high concentrations in synovial fluid of patients with osteoarthritis, TGF beta might play a role in the elevated proteoglycan synthesis and cell proliferation in osteoarthritic cartilage.