Fibronectin (Fn) matrices are vital to vertebrate development and wound healing and modulate tumorigenesis. We used a recombinant Fn-binding integrin, all&, to define rules for integrin-initiated Fn matrix formation. We report the following. First, multiple Fnbinding integrins can support matrix assembly; their activation state controls fibrillogenesis. Second, Fn binding to cells expressing an activated integrin is necessary but not sufficient for matrix assembly. Additional “postoccupancy” events involving the integrin p, but not the a subunit, cytoplasmic domain are needed. Third, these postoccupancy events require an intact actin cytoskeleton. We propose a model for integrin involvement in Fn fibrillogenesis that reconciles previous paradoxes and suggests novel approaches to the therapeutic control of Fn matrix assembly.