In our recent papers, we found the presence of serum autoantibody against neuron specific enolase (NSE) in some glaucoma patients and suggested that this antibody might have significant roles in pathogenesis of glaucomatous optic neuropathy. In order to evaluate further the clinical roles of serum autoantibody against NSE in glaucoma, serum autoantibody against NSE was examined by western blot analysis and enzyme-linked immunosorbent assay (ELISA) in 4 patients with ocular hypertension (OH) and 242 patients with glaucoma (normal tension glaucoma [NTG], 73 cases; primary open angle glaucoma [POAG], 169 cases), and the relationships between the titers of anti-NSE antibody and clinical characteristics were evaluated. The titers of anti-NSE antibody showed a regular decreasing pattern with deteriorating visual field losses and glaucoma stages in POAG, especially early and late stages. However, no systematic pattern was observed in NTG. Although maximum and mean intraocular pressures (IOP)s and progression of visual field losses showed no correlation with the levels of serum anti-NSE antibody titers in either POAG or NTG, the anti-NSE antibody titers were relatively higher in NTG with visual field deterioration than in those without it. The present observations suggest that serum autoantibody against NSE may be clinically useful for diagnosing early stages of POAG, and for monitoring glaucoma progression of NTG.