REGULATED adhesion of T cells to extracellular matrix (ECM) proteins is likely to be essential in T cell migration. Constitutive binding of various other cell types to ECM components is mediated by members of the VLA (very late antigen) subfamily of integrins1-4. We describe here the regulated binding of resting CD4+ human T cells to ECM through three VLA integrins: VLA-4 (refs 5, 6) and VLA-5 (réf. 7) binding to fibronectin (FN), and a novel pathway of VLA-6 binding to laminin (LN). Binding to ECM is regulated in two ways. First, unlike other VLA-mediated interactions, VLA binding activity of the T cells is rapidly and dramatically augmented with cell activation without change in level of expression of the VLA molecules. Second, binding is regulated with T-cell differentiation ; memory T cells express three- to fourfold more VLA-4, VLA-5, and VLA-6 than do naive cells, and bind more efficiently through them to FN and LN.