Abstract Cell-cell and cell-extracellular matrix interactions are mediated by a wide array of cell surface molecules known as adhesion receptors, including the integrin family that comprises numerous alpha beta heterodimers. A new integrin group, the beta 7 subfamily, has been recently defined. Its two members, alpha 4 beta 7 and alpha H beta 7, are involved in the lymphocyte migration to the Peyer's patches and the intestinal mucosa, respectively. We have analyzed the expression of alpha 4 beta 7 integrin on B cells from different cellular compartments and at different activation states. Resting peripheral blood B lymphocytes constitutively express large amounts of alpha 4 beta 7. By contrast, alpha 4 beta 7 integrin, which is absent on resident B cells from different lymphoid tissues, is induced upon activation. Functional studies indicates that alpha 4 beta 7 is mediating B cell attachment to fibronectin and vascular cell adhesion molecule-1 through distinct epitopes on this integrin. Furthermore, the alpha 4 beta 7 integrin is also implicated in intercellular interactions as deduced by the ability of anti-alpha 4 beta 7 mAb to trigger homotypic B cell aggregation. Finally, alpha 4 beta 7 and alpha 4 beta 1 integrins redistribute at the cell membrane in a similar clustering pattern when B cells attach to fibronectin- and vascular cell adhesion molecule-1-coated surfaces. Our studies demonstrate the differential regulation on the expression and function of alpha 4 beta 7 integrin among different human B cell populations.