Stimulation of the CD3/TCR results within minutes in an increase in T cell adhesion to fibronectin. The biochemical pathways that control TCR-mediated increases in adhesion to fibronectin remain poorly characterized. In this study, the role of the tyrosine kinase in the regulation of adhesion by the CD3/TCR was investigated. CD3 stimulation enhanced adhesion to fibronectin on Jurkat T cells line. Tyrosine kinase inhibitor, PP2, and anti β₁ integrin mAb blocked adhesion to fibronectin enhanced by CD3 stimulation on Jurkat T cells. CD3 stimulation did not increase adhesion to fibronectin of the tyrosine kinase ZAP-70-deficient Jurkat T cells line, P116. Furthermore, CD3 stimulation failed to tyrosine phosphorylation of PI3-kinase enzyme AKT on P116 cells. These observations support a model in which the tyrosine kinase activity of ZAP-70 kinase is critical for regulation of β₁ integrin activity by CD3/TCR.