A number of large multidomain extracellular matrix glycoproteins, including fibronectin and members of the tenascin and thrombospondin families, are expressed in locations that suggest they may be involved in the process of chondrogenesis. During early limb morphogenesis, tenascin-C is selectively associated with condensing chondrogenic mesenchyme. With progressive development of endochondral bones, tenascin-C is absent from the matrix surrounding proliferating and hypertrophic chondrocytes, but remains in a restricted distribution in peripheral epiphyseal cartilage. During long bone development, patterns of expression of tenascin-C splice variants differ between chondrogenic and osteogenic regions, suggesting that different isoforms may have different functional roles. Tenascin-C presented as a substratum for chick wing bud mesenchymal cells induces chondrogenic differentiation. In early studies, fibronectin was found to inhibit chondrogenesis, despite being abundant in early chondrogenic mesenchyme. Recent studies showing differential effects of fibronectin splice variants on prechondrogenic mesenchymal condensation may explain this paradox. Members of the thrombospondin gene family are expressed in chondrogenic tissues at different stages, suggesting that they each play a unique role in cartilage development.