What mechanisms regulate endothelial glutathione (GSH) during inflammation? Addressing this question is critical in understanding mechanisms leading to endothelial dysfunction and cardiovascular disease. Herein, the authors show data that support the hypothesis that the intercellular cell adhesion molecule-1 (ICAM-1) regulates GSH. Ligating either constitutive or induced ICAM-1 on the endothelial surface, or exposing endothelial cells to soluble ICAM-1, increases GSH concentrations. ICAM-1 is important in mediating leukocyte adhesion and modulates endothelial signaling pathways important in controlling transmigration. The present data underscore a novel function for ICAM-1 in modulating GSH metabolism and raise the hypothesis that this adhesion molecule controls endothelial redox status under basal and inflammatory conditions. Antioxid. © Mary Ann Liebert, Inc.