OBJECTIVE: To study serum titers of antibodies against heat shock proteins in glaucoma patients from two different ethnic populations and to examine the relationship between serum antibody titers and glaucomatous damage. STUDY DESIGN: Comparative, cross-sectional study. PARTICIPANTS: Twenty-seven age-matched patients with primary open-angle glaucoma, 28 patients with normal pressure glaucoma, and a control group of 26 healthy subjects from Japan; and 21 age-matched patients with primary open-angle glaucoma, 40 patients with normal pressure glaucoma, and a control group of 20 healthy subjects from the United States. MAIN OUTCOME MEASURES: Measurement of serum antibody titers and examination of optic disc and visual field parameters. METHODS: Serum immunoreactivity against heat shock proteins, including hsp27, alphaB-crystallin, and human and bacterial hsp60, was studied by enzyme-linked immunosorbent assay (ELISA). The relationship of serum antibody titers to glaucoma parameters, including mean deviation, neural rim area-to-disc area ratio, and peripapillary atrophy area-to-disc area ratio was examined. RESULTS: The serum ELISA titers of antibodies, including hsp27, alphaB-crystallin, human hsp60, and bacterial hsp60 antibodies, were higher in glaucoma patients compared with control subjects in both the Japanese and American groups (P: < 0.05). There was no association between the serum antibody titers and optic disc parameters in either group from Japan or the United States (P: > 0.05). CONCLUSIONS: These findings suggest that increased titers of circulating antibodies against heat shock proteins occur in both Japanese and American patients with glaucoma. The lack of a relationship between the level of serum antibody titers and the degree of glaucomatous damage in either ethnic group suggests that increased antibodies to heat shock proteins do not occur as an epiphenomenon of the glaucomatous neurodegeneration process.