Human fibroblasts were shown to enhance the proliferation of peripheral T cells in the presence of suboptimal concentrations of anti-CD2 antibodies (anti-T112 and anti-T113) and agonistic anti-VLA-4 antibody. Evidence is provided that the interaction of VLA-4 with immobilized fibronectin can enhance the proliferation of T cells subjected to suboptimal stimulation via CD2. Our results suggest that the fibroblast-stimulated T cell proliferative response to low doses of anti-T112 and T113 antibodies is due to the interaction of VLA-4 with fibroblast fibronectin. These findings also suggest a role for the fibronectin/VLA-4 interaction in the inflammatory process.