Using the technique of in vitro enzymatic DNA amplification and dot blot hybridization with sequence-specific oligonucleotide (SSO) probes, a study of genetic polymorphism of HLA-DPB1 was performed in 83 unrelated patients with Graves' disease (GD), 48 patients with early onset myasthenia gravis (EOMG) and 100 normal British caucasoid subjects who were also tissue typed for HLA-A, B and DR antigens. HLA-DPB 1*0401 was the commonest allele in both patient and control groups with gene frequencies of 0.380, 0.333 and 0.445 for GD, EOMG and controls, respectively. No significant independent association was found with any HLA-DPB 1 allele. As expected, HLA-DR17 is significantly associated with Graves' disease (pc<8×10-3, RR = 2.9), while both HLA-B8 and DR17 are significantly associated with EOMG (pc<2×10-7, RR= 10.3 and pc<0.02, RR = 3.4, respectively)] HLA-DR2 is also significantly increased in EOMG patients who were negative for HLA-DR17 (pc<0.02, RR = 6.4). In addition, the co-occurrence of HLA-B8 with DPB 1*0402 was significantly commoner in patients with GD (p<0.021, RR = 6.2) and EOMG (p<0.0007, RR = 10.8) than in controls, although the HLA-DPB 1 *0402 by itself showed no significant increase.