PURPOSE: We hypothesize that cellular immunity may have a previously unrecognized role in glaucomatous optic neuropathy. The purpose of this study is to analyze subsets of T cells and the levels of cytokine IL-2 and the soluble IL-2 receptor in peripheral blood from patients with normal pressure glaucoma (NPG) or primary open angle glaucoma (POAG) in comparison to age-matched control subjects. METHODS: In this study, 38 patients (20 NPG; 18 POAG) and 19 controls were included. sIL-2R and IL-2 were assayed by ELISA. T cell subsets were analyzed by flow cytometry and lymphocyte proliferation was used to measure the reactive ability of T cells to phytohemagglutinin (PHA). RESULTS: The frequency of CD8+HLA-DR+ lymphocytes were increased in patients with NPG (P = 0.008), and CD3+CD8+ lymphocytes increased in both NPG (P = 0.03) and POAG patients (P = 0.0004). CD5+ lymphocytes were higher only in POAG patients (P = 0.0012). In comparison to controls, the ratio of CD4+/CD8+ lymphocytes was similar in both groups. The mean concentrations of sIL-2R in NPG (P = 0.011) and POAG (P = 0.0023) patients were higher than that found in control subjects although IL-2 concentrations were similar in these groups. In addition, the reactive ability of T lymphocytes to the non-specific reagent (PHA) was reduced significantly in NPG (P = 0.02) and POAG patients (P=0.04). CONCLUSION: The alterations of the cellular immune system in patients with glaucoma support our hypothesis that the immune system may play an important role in the initiation and/or sustainment of glaucomatous optic neuropathy in some patients.