Clinical and laboratory findings of autoimmunity are common in chronic hepatitis C. Autoimmune hepatitis (AIH), a disease of unknown cause, has been defined by use of the International Autoimmune Hepatitis Group Score (AIH score), which quantifies clinical and laboratory parameters. To further validate the specificity of the International AIH score and investigate the similarities between hepatitis C and AIH, we measured the International Autoimmune Hepatitis Group Score in patients with well-defined chronic hepatitis C. Thirty consecutive non-cirrhotic patients with chronic hepatitis C were evaluated. Scoring was performed using both components of the AIH score: a set of minimum required parameters including laboratory and historical data and a second set of additional parameters dominated by histological criteria. Autoantibodies were positive in 21 of 30 hepatitis C patients and associated (patient or first-degree relative) autoimmune diseases were present in eight of 30 patients. Histologically, chronic active hepatitis with periportal piecemeal necrosis was seen in 24 of 30 patients and lymphoid follicles in 16 of 30 patients. No patient scored as probable or definite AIH using the minimum required parameters of the AIH score. When histological parameters were included, four of 30 patients scored as probable AIH but none as definite AIH. Therefore, AIH was excluded by the minimal and additional criteria of the AIH score in 86% of patients with hepatitis C despite a high prevalence of autoantibodies in these patients. We conclude that the criteria set forth by the International AIH scoring system defines a distinct disease although it shares some features with chronic hepatitis C. Modification of the AIH scoring system to include other commonly accepted risk factors for hepatitis C and additional histological parameters would further improve its specificity.