Development of the mammalian secondary palate requires proper production of the extracellular matrix, particularly glycosaminoglycans (GAGs) and collagen. Endogenous factors that regulate the metabolism of these molecules are largely undefined. A candidate for a locally derived molecule would be transforming growth factor ß1(TGFß1) by virtue of its potency as a modulator of extracellular matrix metabolism by several cell lines. We have thus attempted to assign a regulatory role for TGFß1 in modulation of GAG production and degradation by mesenchymal cells of the murine embryonic palate (MEPM). Treatment with TGFß1 or TGFß2, but not IGF-II, resulted in a stimulation of total GAG synthesis. Furthermore, cells treated with bothTGFß1 and TGFa showed a synergistic increase in GAG synthesis if pretreated with TGFß1 but not TGFa. Simultaneous stimulation with TGFß1 and TGFß2 did not elicit a synergistic response. These studies demonstrate the ability of TGFß, synthesized by embryonic palatal cells, to specifically stimulate GAG synthesis by MEPM cells. Other growth factors present in the developing craniofacial region may also modulate TGFß-induced GAG synthesis, a biosynthetic process critical to normal development of the embryonic palate.