HLA phenotypes and autoantibody responses were studied in 71 Japanese patients with myasthenia gravis. HLA-A2, Bw61, and DRw9 were associated with ocular myasthenia gravis (corrected p [CP] less than 0.05 relative risk [RR] = 2.88; CP less than 0.02, RR = 3.60; and CP less than 0.001, RR = 4.63, respectively) and HLA-DRw8 was associated with generalized myasthenia gravis (CP less than 0.001, RR = 5.40). Neither HLA-B8 nor DR3 was found in Japanese patients. The titer of antiacetylcholine receptor antibody (AChR Ab) and the incidence of autoantibodies other than AChR Ab were higher in patients with generalized myasthenia gravis than in those with the ocular type (2.77 +/- 0.62 versus 0.17 +/- 0.03 pmol/ml, p less than 0.001; and 60.6 versus 29.0%, p less than 0.02, respectively). Patients with a high titer of AChR Ab or with autoantibodies had an increased frequency of HLA-DRw8 (CP less than 0.02, RR = 4.61, and CP less than 0.005, RR = 4.53, respectively); whereas patients with a low titer of AChR Ab or without autoantibodies had an increased frequency of HLA-DRw9 (CP less than 0.001, RR = 8.26, and CP less than 0.005, RR = 4.08, respectively). These findings suggest that ocular and generalized myasthenia gravis might have different immunogenetic backgrounds.