OBJECTIVE The aim of this study was to investigate the associations between major histocompatibility complex (MHC) class I and II alleles and disease characteristics in Turkish patients with myasthenia gravis (MG). METHODS The MHC class I and II alleles of 108 unrelated MG patients were genotyped. The human leucocyte antigen (HLA) distribution of all MG patients and subgroups of MG patients (grouped according to disease characteristics) was compared to that of 250 healthy controls. RESULTS Overall distributions of HLA-B*61 and C*05 were more frequent in MG patients (7.4 vs. 2.0% and 14.8 vs. 6.8%, respectively) than in non-MG patients. Subgroup analyses revealed that HLA-DRB1*14 and DQB1*02 alleles were more frequent in early-onset MG [n = 10 (20.8%) vs. n = 25 (10.0%) and n = 21 (43.8%) vs. n = 59 (23.6%)]. In patients seropositive for anti-AchR antibodies, the frequencies of HLA-B*50 and C*05 were higher. HLA-C*05, DRB1*01, and DRB1*11 were higher in patients with ocular MG. In addition, HLA-A*01, A*31, B*08, and DRB1*14 were higher among patients with thymic hyperplasia, whereas DQB1*03 was lower. However, all of these differences lost significance after correction of the p value for multiple comparisons. No allele association was found among patients with thymoma. Strikingly, patients with generalized MG who had pure ocular symptoms at disease onset had significantly increased HLA-B*50 compared to the controls (corrected p < 0.001, OR = 9.92; 95% CI 3.05-32.22). CONCLUSIONS The HLA-B*50 allele was associated with conversion to generalized disease in patients with pure ocular symptoms at disease onset. This finding could extend our understanding of the complex interactions between the pathogenesis of MG and genetic heritage.