We determined antigens of the major histocompatibility complex classes I, II, and III in 25 families of Mexican mestizo glaucomatous patients. Patients and family members were examined, and the predisposition of first-degree relatives to a corticosteroid-provocative test was determined. The results showed a high frequency of the HLA-DR3 antigen in patients with primary open-angle glaucoma compared with controls (32.5% vs 4.0%, P = .001, odds ratio = 10.25). We suggest that the increased presence of the HLA-DR3 antigen could be an important factor in the genetic susceptibility to glaucoma.