It is well known that cellular interactions, such as cell adhesion, migration, invasion, between cells and the extracellular matrix are mediated by the integrin family of cell surface receptors. Chondrocytes are surrounded by an abundant extracellular matrix, but there is less information on the cellular receptors which interact with this matrix. In our studies, fibronectin, type I collagen, and type II collagen promoted haptotactic and chemotactic migration of chondrocytes, as determined using a modified Boyden chamber system. Treatment of chondrocytes with tyrosine kinase inhibitor, herbimycin or genistein, resulted in a dose dependent inhibition of migration toward these matrix proteins, whereas adhesion of chondrocytes was not influenced. This indicated the existence of functional relationships between protein tyrosine phosphorylation and chondrocyte migration following the adhesion of chondrocytes to matrix proteins. Further study showed that the peptide GRGDSP inhibited chondrocyte migration to fibronectin but not to collagens. On the other hand, chondrocytes migrated toward the tetra-RGD containing peptide, but not the peptide GRGDSP, in a dose dependent fashion. These observations suggest that cross-linking or clustering of integrins is essential to induce transmembrane signaling related to tyrosine phosphorylation for chondrocyte migration toward fibronectin.