We investigated the HLA-DPB1 allele in 43 unrelated Japanese patients with myasthenia gravis (MG) using digestion of polymerase chain reaction (PCR)-amplified DNA with allele-specific restriction endonucleases (PCR-RFLP method). We found a higher frequency of the DPB1*0201 allele in female patients whose ages at onset were less than 30 years (83.3%) than in controls (35.6%). The study also included serologic typing of HLA-A, -B, -C, and -DR antigens in 72 patients with MG, and confirmed previous results demonstrating a strong association of HLA-DR53 with early onset of MG in females. These results indicate that both the DPB1*0201 allele and DR53 play key roles in the disease process of MG in early-onset females, and that the genetic background of Japanese females with early-onset MG is different from that of other patients with MG.