In order to investigate the role of immunogenetic factors in the pathogenesis of uveitis in leprosy, human leukocyte antigens (HLA) were analyzed among leprotics with and without uveitis. The subjects were 85 Japanese leprosy patients, 44 with uveitis and 41 without uveitis. Controls were 138 healthy subjects. A modified two-stage complement dependent microcytotoxicity test was used for typing HLA-A, -B, -C, -DR and -DQ antigens. The occurrence of HLA-DR2 antigen was significantly increased in patients as a whole (69.4%), and in the patients with uveitis (79.5%) as compared with the control subjects (35.5%). The association with DR2 was even stronger in the patients with uveitis (odds ratio = 7.1, Pc < 0.000005) than in the patients as a whole (odds ratio = 4.1, Pc < 0.0001). On the other hand, HLA-DR53 antigen was significantly decreased in the patients as a whole (43.5%) and in the patients with uveitis (36.4%) as compared with the control subjects (69.6%). No significant difference in the distribution of HLA antigens was observed in the patients without uveitis. Our results suggest that HLA-DR2 contributes to the susceptibility to uveitis in Japanese leprosy patients.