Objective - To investigate the association of complement C4 allotypes with rheumatoid arthritis in Koreans. Methods - 65 rheumatoid arthritis patients and 255 controls were typed for C4 allotypes and HLA-A, B, C, DR, and DQ antigens. Results - The frequencies of C4AQO (32.3% v 14.9%, P < 0.005) and C4B5 (29.2% v 12.2%, P < 0.005) were significantly increased in rheumatoid arthritis patients compared with healthy control subjects. Among rheumatoid patients, the frequency of C4AQO was significantly increased in both the rheumatoid factor (RF) positive (27.3%) and the RF negative (66.7%) subgroups. The frequencies of C4B5 and HLA-DR4 were significantly increased only in RF positive subgroup. C4B5 was strongly associated with MLA-DR4, whereas C4AQO did not show association with DR4. Conclusions - In Koreans, C4AQO and C4B5 are associated with susceptibility to rheumatoid arthritis, as in the Japanese. C4B5 is strongly associated with HLA-DR4. C4AQO is considered to be a DR4 independent risk factor, and a disease susceptibility allele in linkage disequilibrium with C4AQO is suggested in Korean patients with rheumatoid arthritis.