The recruitment of eosinophils to sites of allergic inflammation in vivo is a multistep process characterized by initial eosinophil intravascular tethering and firm adhesion to endothelium, followed by sequential eosinophil diapedesis between endothelial cells and chemotaxis into tissues (1–3). The selective tissue recruitment of eosinophils is controlled by multiple factors, including the profile of eosinophil adhesion receptors, the density of their ligands expressed on endothelial cells, as well as the tissue-and disease-induced expression patterns of chemokines. The importance of eosinophil and endothelial cell adhesion receptor interactions to eosinophil recruitment in vivo is suggested from studies using animal models of allergic inflammation in which inhibition of either eosinophil or endothelial adhesion molecules significantly reduces eosinophil tissue recruitment (4–6). Studies using intravital videomicroscopy to visualize eosinophil endothelial interactions under conditions of blood flow in vivo have confirmed that eosinophil adhesion to endothelium occurs via a series of discrete steps, which include initial eosinophil tethering to endothelium, activation-dependent adhesion, and transendothelial migration (7–10). The eosinophil adhesion receptors subserving these functions in vivo have been identified in mice treated with neutralizing antibodies to adhesion molecules, or in adhesion molecule–deficient mice. These eosinophil adhesion receptors comprise receptors allowing eosinophils to tether to endothelium (L-selectin, PSGL-1, 4 1, 4 7)(7–10) and receptors mediating eosinophil firm adhesion to endothelium (2 integrin, 4 1, 4 7)(10). Although in vitro and in vivo studies have provided important insight into the receptors used by eosinophils to tether to, and to firmly adhere to, endothelium, more recent studies are providing insight into the signals that mediate the ability of eosinophils to rapidly change from rolling along the endothelial surface of a blood vessel to firmly adhering to the interior of the blood vessel and subsequently transmigrating into tissues. Progression of circulating leukocytes, including eosinophils, from the bloodstream into inflamed tissues, occurs by a defined sequential series of activation and adhesion steps to endothelium. A variety of different chemotactic mediators (eotaxin, PAF, IL-8, LTB4, C5a, FMLP) can induce activation-dependent adhesion of leukocytes to endothelium under flow conditions in vitro (11–13). These chemotactic mediators probably act through a common leukocyte cellular signaling mechanism, as all the aforementioned chemotactic mediators bind to seven transmembrane receptors coupled to the pertussis toxin–sensitive subunit of the G protein Gi (Gi a)(14, 15). Chemokines can potentiate VLA-4–mediated tethering to endothelium within 0.1 s of contact through Gi protein signaling (16). Interestingly, in the absence of G (q) signaling, eosinophils failed to accumulate in the lungs following allergen challenge, which is attributed to the failure of hemopoieticallyderived cells to elaborate GM-CSF in the airways (17). In studies using a single cell adhesion assay, GM-CSF has also been shown to upregulate the biophysical strength of eosinophil adhesion to VCAM-1, suggesting another pathway for G (q) signaling to influence eosinophil adhesion to endothelium (18). Although activation-dependent arrest of rolling leukocytes has been a part of the paradigm of leukocyte recruitment for many years, in vivo evidence to support the hypothesis that endothelial proteoglycans present chemokines to rolling leukocytes in vivo is not yet available. The current paradigm suggests that chemokines released locally at sites of …