Chronic hepatitis C virus (HCV) has been linked to extrahepatic autoimmune phenomena. In addition a variety of autoantibodies were found in patients with HCV. This study was performed to assesss the clinical relevance of antikeratin antibodies in rheumatoid arthritis (RA) and in patients with symmetric polyarthritis associated with hepatitis C infection. Serum antikeratin antibodies were evaluated in 3 different groups of patients; all were rheumatoid factor (RF) seropositive: Group 1: 31 patients with HCV associated symmetric polyarthralgia or arthritis. Group 2: 28 patients with RA (modified ACR criteria for probable RA). Group 3: 16 patients with autoimmune disorders other than RA. Seventeen healthy individuals matched for age and sex served as controls. In our study, 75 patients who were rheumatoid factor positive (measured by ELISA, the cutoff was established to 20 U/mL) were tested for antikeratin antibodies using an indirect immunofluorescence technique with 1:10 serum dilution. Antikeratin antibodies were detected in 18/28 (64%) patients with true RA and only 3/31 (9%) patients with HCV-related arthritis (p < 0.0001). Antikeratin antibodies were observed in 3/16 (18%) patients of group 3 (p < 0.05). Antikeratin antibodies were not found in the sera of the healthy controls.