• Serum addition to stationary chick embryo fibroblasts in vitro causes a 300% increase in acid mucopolysaccharide production, this increase being linear both with time and concentration of serum added. At the same time, serum-stimulated production is reduced in cells which are actively dividing. The increase in acid mucopolysaccharide production caused by serum is in some manner dependent upon RNA synthesis, since the addition of actinomycin D reduces its effect by 50% within 4 h. A correlation between acid mucopolysaccharide production and chondroitin sulphotransferase activity (EC 2.8 2.5, 3'-phosphoadenyl 5'-phosphosulphate: chondroitin sulphotransferase) is seen. Both increase to over 400% of control values 24 h after serum addition, and both are sensitive to the presence of actinomycin D. • Serum control over production of these extracellular molecules is demonstrated and may be linked to the mitotic activity of the cell. It is proposed that this control by serum over acid mucopolysaccharide production can provide one mechanism for the cell to alter its external environment and thus affect events such as cell to cell interactions and hormonal signals necessary to cellular functions.