Glucocorticoid induced tumor necrosis factor receptor (GITR) is a new member of the tumor necrosis factor^nerve growth factor receptor superfamily of which the function has not been well studied. The extracellular domain of GITR was produced in Escherichia coli and purified as a single band of predicted M r of 18.0 kDa. GITR and GITR ligand were expressed constitutively on the surface of Raw 264.7 macrophage cell line and murine peritoneal macrophages. An extracellular domain of GITR can activate murine macrophages to express inducible nitric oxide synthase and to generate nitric oxide in a dose-and time-dependent manner. ß