Purpose To study the frequencies of human leukocyte antigen (HLA) specificities in Italian patients with Vogt-Koyanagi-Harada disease and to correlate the presence of each specificity to the clinical features. Methods Human leukocyte antigen specificities were determined by standard microlymphocytotoxicity assay in 16 patients with Vogt-Koyanagi-Harada disease and compared with HLA specificities of 116 healthy controls. Results HLA-DR4 was statistically related to Vogt-Koyanagi-Harada disease (P = .0063), whereas only a trend toward a significant association between the disease and HLA-B41 was found (P = .06). HLA-DQ1 was detected in a disproportionate number of controls (68.9%) compared with patients (37.5%). Conclusions HLA-DR4 was significantly related to Vogt-Koyanagi-Harada disease in Caucasian European patients, specifically in Italian patients, as it was described in other racial groups. No clear relation was found between the ophthalmologic and systemic manifestations of Vogt-Koyanagi-Harada disease and the presence of HLA specificities.