The α4 integrin LPAM‐1 (α4β7) mediates lymphocyte attachment within the extracellular matrix (ECM) by adhering to the connecting segment (CS)‐1 site of fibronectin (FN). Here we reveal that very late antigen (VLA)‐4⁻ LPAM‐1⁺ T cell lymphoma TK‐1 cells bind via LPAM‐1 to multiple copies of the RGD sequence engineered within an FN‐like polymer. Further, the small conformationally restrained RGD‐like cyclic peptides 1‐adamantaneacetyl‐Cys‐Gly‐Arg‐Gly‐Asp‐Ser‐Pro‐Cys and Arg‐Cys‐Asp‐thioproline‐Cys inhibit the adhesion of TK‐1 cells to immobilized CS‐1 peptide, and to endothelial counterreceptors for LPAM‐1, namely mucosal addressin cell adhesion molecule (MAdCAM)‐1 and vascular cell adhesion molecule (VCAM)‐1. Spontaneous adhesion of the VLA‐4⁻ LPAM‐1⁺ B lymphoma cell line RPMI 8866 to CS‐1 was likewise inhibited, confirming a previously undocumented ability of LPAM‐1 to recognize the RGD tripeptide. The RGD‐binding site in LPAM‐1 either overlaps or is identical to sites required for interaction with MAdCAM‐1, VCAM‐1, and the CS‐1. The binding of LPAM‐1 and VLA‐4 to RGD‐containing ligands may have relevance in vivo given that fibrinogen at physiological concentrations is able to partially block the binding of TK‐1 cells to MAdCAM‐1. Hence fibrinogen and other vascular RGD‐containing proteins may have mild anti‐inflammatory activity required for maintaining effective homeostasis, analogous to the anti‐thrombogenic activity of the vascular endothelium.