Human leukocyte antigen typing was performed in 32 consecutive Chinese patients with Vogt-Koyanagi-Harada syndrome and 52 unrelated healthy Chinese individuals. Results indicated that HLA-DR4 was identified in 24 of the 32 patients with Vogt-Koyanagi-Harada syndrome (75.0%), but only in 12 (23.1%) of the 52 control subjects (P = .0003; relative risk, 10.0). Human leukocyte antigen-DQw7, also correlated with the disease, was identified in 19 (59.4%) patients, and in 19 control subjects (36.5%; P = .0230). The two-haplotype association detection demonstrated that HLA-DR4 and HLA-DQw7 were related through linkage disequilibrium, suggesting that the disease was primarily associated with only one of the antigens. The comparison between HLA-DR4-positive and HLA-DR4-negative patients with Vogt-Koyanagi-Harada syndrome in regard to clinical manifestations has shown that the HLA-DR4-positive group had a lower visual acuity at the first visit than did the HLA-DR4-negative group. However, both groups responded well to corticosteroid treatment. No other significant correlations between HLA-DR4 positivity and ocular features, including complications or systemic features, were found. Therefore, we concluded that the presence of HLA-DR4 may represent susceptibility to Vogt-Koyanagi-Harada syndrome, but may not represent specific tissue involvement or determine the prognosis. A decreased frequency of HLA-DQw1 in the patient group was also noticed. Further studies showed a higher percentage of HLA-DQw1 in HLA-DR4-positive control subjects than in the HLA-DR4-positive patients (P = .0308), which indicated that HLA-DQw1 was negatively associated with the disease. This protective effect from HLA-DQw1 was also studied.