Transforming growth factor-β (TGFβ) is a local regulator of cell metabolism and growth. TGFβ increases the synthesis of collagen and enhances the deposition of matrix by almost all cells studied to date. The presence of TGFβ in cartilage suggests an important autocrine function, and the present study was designed to examine its influence on the matrix synthesis of chick epiphyseal chondrocytes. Chondrocytes were plated in serum-free (BSA-supplemented) medium or medium containing 10% fetal bovine serum (FBS), and after 24 h in monolayer culture were treated with TGFβ in identical medium. A 24-h incubation with TGFβ caused a dose-dependent decrease in collagen synthesis (–14%) and increase in noncollagen protein synthesis (+25%), with greater effects in serumcontaining medium (–22% and +58%, respectively). Similarly, the stimulation of sulfate incorporation by TGFβ was greater in FBS-containing medium (+140%) than in serum-free medium (+70%). These changes were present by 6 h, were maximal in the 0.3–3.0 ng/ml dose range, and were found to reflect an alteration in extracellular protein synthesis. The enhancement of TGFβ effects by serum was abolished when chondrocytes were plated and exposed to TGFβ in medium containing dialyzed FBS (12–14K membrane). The present study indicates that TGFβ influences the synthesis of matrix components by growth plate chondrocytes. The effects are enhanced by factors present in serum.