OBJECTIVE: Rheumatoid arthritis (RA) is the most common rheumatic disease but its diagnosis primarily relies on clinical disease manifestations. The serologic support is restricted to the determination of rheumatoid factor (RF), of which diagnostic ability is far from satisfaction. We compared the usefulness of a new serologic test, anti-cyclic citrullinated peptide antibodies (anti-CCP) for the diagnosis of RA with RF. METHODS: Anti-CCP antibodies were determined in 220 serum samples; 134 from RA patients and 86 from controls including 33 healthy controls and 53 patients with other diseases. Of 33 sera of the healthy controls, 12 were RF positive, which were intentionally included for the better analysis of specificities. Anti-CCP was done with the enzyme-linked immunosorbent assay (ELISA). RF was also assayed in every sample, and results were compared to anti-CCP for sensitivity and specificity. RESULTS: On each receiver operating characteristic curve, the area of under the curve was 0.843+/-0.028 for anti-CCP and 0.741+/-0.033 for RF. At each optimum cut-off value, the sensitivity of anti-CCP was comparable to that of RF (76.1% vs 67.2%) and the specificity of anti-CCP was better than that of RF (94.2% vs 74.4%, p<0.001). Importantly, 18 of 38 (47.4%) sera from RA patients negative for RF were positive for anti-CCP. Only one of 12 sera from healthy controls positive for RF was positive for anti-CCP. CONCLUSION: The anti-CCP ELISA showed high sensitivity even in RF negative RA patients, and very high specificity in healthy controls and disease control groups. The anti-CCP ELISA appeared a very useful new diagnostic test for RA. ivity.