Leukocytes extravasate from the blood into inflammatory sites through complementary ligand interactions between leukocytes and endothelial cells, Activation of T cells increases their binding to hyaluronate (HA) and enables CD44-mediated primary adhesion (rolling). This rolling could be induced in vivo in murine V(beta)8(+) T cells in response to specific superantigen stimulation; it was initially found in lymph nodes, then in peripheral blood, and finally within the peritoneum, the original inflamed site. The migration of V(beta)8(+) cells into the peritoneal cavity was dependent on CD44 and HA, as shown by inhibition studies. Thus, CD44-HA interactions can target lymphocytes to specific extralymphoid effector sites.