The expression of the glucocorticoid induced TNF receptor family related gene (GITR) in subsets of T lymphocytes from human peripheral blood was studied. In normal human peripheral blood mononuclear cells, GITR expression on the resting CD4+ T cells was low but markedly increased after activation. The percentage of GITR+ T cells in the CD4+CD25+ T cell subpopulation (15.1%) was significantly higher than that in the CD4+CD25- T cell subpopulation (5.2%, P<0.01), suggesting a preferential co-expression of GITR with CD25. In a group of patients with non-infectious uveitis, a proposed T helper cell mediated autoimmune ocular disease, the GITR expression on the CD4+ T cells in both the active patients (34.5%) and the inactive patients (19.6%) was significantly higher as compared to that in the normal donors (10.7%; P<0.01 vs. active, P<0.05 vs. inactive). This increased GITR expression in T cells was only seen in the CD4 positive T helper cell subpopulation but not in the CD4 negative T cell subpopulation. GITR expression on the CD4+ T cells decreased when the patients became clinically quiescent. Therefore, GITR is an activation marker for the CD4+ T cells and preferentially co-expressed with CD25 on the CD4+ T cells in human peripheral blood. Its expression correlates with the clinical course of non-infectious uveitis.