The polycation, poly(L-lysine), repressed the synthesis of glycosaminoglycans in secondary cultures of chick embryo skin fibroblasts and caused sequestration of glycosaminoglycans around the cells. The synthesis of chondroitin sulphate, dermatan sulphate, hyaluronic acid and a fourth component, thought to be heparan sulphate, were all inhibited to the same extent but the sequestration of the sulphated polymers were greater than that of the unsulphated. The sequestered material was retained around and not within the cells. Incubations with the polyanion, poly(L-glutamate), showed a slight stimulation of glycosaminoglycan synthesis and in these and control incubations (no additions to medium), most of the glycosaminoglycan synthesised appeared in the culture medium. The subsequent addition of poly(L-glutamate) to incubations containing poly(L-lysine) reversed the inhibitory and sequestering effect of the polycation. It was concluded that the inhibition of synthesis by poly(L-lysine) was either a direct effect of poly(L-lysine) on the cell membrane or a result of the high local pericellular concentration of sequestered proteoglycan.