In order to investigate the role of immunogenetic factors in the pathogenesis of uveitis in leprosy, HLA antigens were analyzed between the leprotics with and without uveitis. Sixty-five Japanese leprosy patients comprised 32 with uveitis and 33 without uveitis. Controls consisted of 138 healthy subjects. A lymphocyte cytotoxicity test was used for typing HLA-A, -B, -C, -DR and -DQ antigens. HLA-DR2 genotyping was performed by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and PCR-restriction fragment length polymorphism (RFLP) methods. The frequency of HLA-DR2 antigen was significantly increased in the patients with uveitis as compared with the control subjects (Pc < 0.0005), whereas HLA-DR53 antigen was significantly decreased (Pc < 0.05). At the genomic level the frequency of HLA-DRB1*1501 was significantly increased in the patients with uveitis and without uveitis as compared with that in the controls. The association with DRB1*1501 was even stronger in patients with uveitis (odds ratio = 7.1, Pc < 0.000005) than in the patients without uveitis (odds ratio = 4.1, Pc < 0.005). Our results suggest that HLA-DRB1*1501 contribute to the susceptibility to uveitis in the Japanese with leprosy.